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Ketamine: A review of its pharmacologic properties and use in ambulatory anesthesia
Abstract
The administration of intravenous agents is the most commonly used method in Canada and the United States to produce sedation or general anesthesia for dental procedures. Ketamine, a dissociative anesthetic, has several advantageous physical, pharmacokinetic, and pharmacodynamic properties. It can be used to induce anesthesia, sedation, analgesia, and amnesia. Ketamine can maintain functional residual capacity, induce bronchodilation, and avoid cardiovascular depression. However, adverse effects have been demonstrated, such as cardiovascular stimulation and unpleasant emergence phenomena, both of which may be modulated by supplementation with benzodiazepines. An increase in the use of ketamine for ambulatory anesthesia has recently been advocated. This review of the literature supports the use of ketamine as an effective agent for selected anesthetic procedures.
... Norketamine is subsequently hydroxylated to 6-hydroxynorketamine by CYP2B6 and CYP2A6 enzymes or to dehydroxynorketamine (DHNK) by CYP2B6 (Mion and Villevieille 2013). Elimination occurs through the kidneys after norketamine and other metabolites undergo glucuronide conjugation into water soluble compounds and are finally excreted in the urine and bile, with only a minor percentage of unchanged drug (Haas and Harper 1992). A secondary metabolic pathway is the direct hydroxylation of ketamine to hydroxynorketamine (HNK) and in animal models this may additionally occur in the intestines, liver and lungs (Zanos et al. 2018). ...
... A study on bipolar depression reported evidence of metabolites DHNK and HNK, 3 days after administration, whilst a paediatric study found norketamine was present in the urine 14 days after administration and ketamine 11 days post-administration (Adamowicz and Kala 2005). Furthermore, when compared to adults, children have been shown to metabolise ketamine twice as rapidly (Haas and Harper 1992), suggesting a prolonged exposure to norketamine after oral administration in adults, which may contribute to the therapeutic effect. Additionally, repeated dosing may result in a reduced elimination, with one study of three 0.75-1.59 ...
... However, oral ketamine is more susceptible to individual factors which may affect the bioavailability, including the drug preparation, cytochrome enzyme phenotypes and liver enzyme induction. Ketamine metabolism is a function of liver blood flow with a high hepatic extraction ratio (0.9), and thus, its clearance is sensitive to changes in hepatic blood flow (Haas and Harper 1992). Further factors affecting clearance include the high degree of variability in the expression and catalytic action of the CYP enzymes responsible for ketamine's metabolism in humans (Nottage et al. 2023). ...
Ketamine has received considerable attention for its rapid and robust antidepressant response over the past decade. Current evidence, in clinical populations, predominantly relates to parenterally administered ketamine, which is reported to produce significant undesirable side effects, with additional concerns regarding long-term safety and abuse potential. Attempts to produce a similar drug to ketamine, without the psychotomimetic side effects, have proved elusive. Orally administered ketamine has a different pharmacological profile to parentally administered ketamine, suggesting it may be a viable alternative. Emerging evidence regarding the efficacy and tolerability of oral ketamine suggests that it may be a favourable route of administration, as it appears to obtain similarly beneficial treatment effects, but without the cost and medical resources required in parenteral dosing. The pharmacological effects may be due to the active metabolite norketamine, which has been found to be at substantially higher levels via oral dosing, most likely due to first-pass clearance. Despite bioavailability and peak plasma concentrations both being lower than when administered parenterally, evidence suggests that low-dose oral ketamine is clinically effective in treating pain. This may also be due to the actions of norketamine and therefore, its relevance to the mental health context is explored in this narrative review.
... Given its safe profile, it can be used as an in-hospital and out-hospital anesthetic agent for emergencies, disaster situations and in third world countries. It can also be used for the management of complex chronic pain and as an antidepressant [3,4,5]. ...
... A systematic review, studying the effect of chronic ketamine use on the brain, suggests that high dose and +Model TOXAC-455; No. of Pages 11 A. Hottat and P. Hantson long term-term ketamine use could affect the structure and function of cortical gray and white matter, especially in the fronto-parietal regions [3,4]. ...
... The structural and functional changes observed in studies seem to correlate with the duration and dose of ketamine consumption and are even more objectifiable after 3 years of high dose ketamine use [3,4]. ...
... [8,9] Thus, ambulatory cleft lip repair (CLR) under ketamine sedation has been in ascendency in the global community. [5,7,8,10] However, across Africa including Nigeria, there is dearth of studies probing its safety and practicability. Therefore, the purpose of this research was to scrutinize the feasibility of ambulatory CLR at Usmanu Danfodiyo University Teaching Hospital (UDUTH), Sokoto, Nigeria. ...
... [5] Ketamine is a structural analogue of phenycyclidine (arylcyclohexylamine), consists of racemic mixture of two enantiomers S(+) and R (-); and highly lipophilic. [10,15,18,22,30] It binds multiple sites but principally noncompetitively antagonize N-methyl-D-aspartate (NMDA) receptor. [10,18,30] Other sites include non-NMDA glutamate receptors, nicotinic/ muscarinic cholinergic receptors, µ and κ receptors and sodium, potassium and calcium channel. ...
... [10,15,18,22,30] It binds multiple sites but principally noncompetitively antagonize N-methyl-D-aspartate (NMDA) receptor. [10,18,30] Other sites include non-NMDA glutamate receptors, nicotinic/ muscarinic cholinergic receptors, µ and κ receptors and sodium, potassium and calcium channel. Mechanism of action is primarily on the cortical and limbic systems causing functional dissociation (cataleptic state, cardiovascular stability, protective airway maintenance, bronchodilation, sedation, analgesia and amnesia). ...
... [8,9] Thus, ambulatory cleft lip repair (CLR) under ketamine sedation has been in ascendency in the global community. [5,7,8,10] However, across Africa including Nigeria, there is dearth of studies probing its safety and practicability. Therefore, the purpose of this research was to scrutinize the feasibility of ambulatory CLR at Usmanu Danfodiyo University Teaching Hospital (UDUTH), Sokoto, Nigeria. ...
... [5] Ketamine is a structural analogue of phenycyclidine (arylcyclohexylamine), consists of racemic mixture of two enantiomers S(+) and R (-); and highly lipophilic. [10,15,18,22,30] It binds multiple sites but principally noncompetitively antagonize N-methyl-D-aspartate (NMDA) receptor. [10,18,30] Other sites include non-NMDA glutamate receptors, nicotinic/ muscarinic cholinergic receptors, µ and κ receptors and sodium, potassium and calcium channel. ...
... [10,15,18,22,30] It binds multiple sites but principally noncompetitively antagonize N-methyl-D-aspartate (NMDA) receptor. [10,18,30] Other sites include non-NMDA glutamate receptors, nicotinic/ muscarinic cholinergic receptors, µ and κ receptors and sodium, potassium and calcium channel. Mechanism of action is primarily on the cortical and limbic systems causing functional dissociation (cataleptic state, cardiovascular stability, protective airway maintenance, bronchodilation, sedation, analgesia and amnesia). ...
Objective
To report the applicability of ambulatory cleft lip repair (CLR) and to review the existing literature.
Materials and Methods
This is a retrospective clinical case series study of ambulatory CLR in North-western Nigeria. The study was carried out in Usmanu Danfodiyo University Teaching Hospital (UDUTH), Sokoto, between January 2012 and December 2018. Relevant clinical data of the subjects obtained include sociodemographics, type of cleft, and complications. Protocol employed includes premedication with diazepam (0.5 mg/kg, IV) slowly, followed by administration of glycopyrrolate (0.005 mg/kg, IV) and diclofenac potassium (1 mg/kg, IV). Then, ketamine (0.1 mg/kg, IV) was infused slowly over a 5-min period to achieve procedural sedation (Ramsey sedation score of 3). The data were analyzed using (SPSS; Chicago, IL, USA) program, version 20. The results were presented in simple descriptive statistics.
Results
The age ranged from 2 to 21 years with male preponderance (M: F = 4:1). All participants had unilateral clefts lip with or without alveolus. The left side was twice involved as the right. There were no perioperative complications nor mortality recorded and no patient required conversion to general anesthesia. All patients were successfully discharged home on the same day of the operation. No case of readmission was recorded and subsequent follow-up was uneventful.
Conclusions
Parenteral use of ketamine and diazepam for outpatient pediatric cleft lip procedures is safe and of immense benefits in reducing the surgical cleft burden without compromising patients safety.
... Ketamine, an anaesthetic with analgesic properties, is a racemic mixture composed of esketamine (S-ketamine) and arketamine (R-ketamine). It has a long history of use in anaesthesiology and emergency medicine (Domino, 1980;Haas and Harper, 1992), and its mechanism of action through NMDA receptors is well-documented (Jelen et al., 2021;Mihaljević et al., 2020). However, the pharmacodynamic and pharmacokinetic properties of ketamine enantiomers have only been subject to more intensive research in recent years. ...
... U pacjentów z TRD, u których augmentacja wspomnianymi lekami nie przynosi efektów terapeutycznych, w świetle rosnącej liczby dowodów odpowiedzią może być ordynowanie ketaminy lub jej enancjomerów. Ketamina, anestetyk z komponentą przeciwbólową, będący racematem esketaminy (S-ketamina) i arketaminy (R-ketamina), jest substancją o długiej historii stosowania w anestezjologii i ratownictwie (Domino, 1980;Haas and Harper, 1992), a jej mechanizm działania przez receptory NMDA jest dobrze udokumentowany (Jelen et al., 2021;Mihaljević et al., 2020). Jednak właściwości farmakodynamiczne i farmakokinetyczne enancjomerów ketaminy zaczęto intensywniej oceniać dopiero w ostatnich latach. ...
... Ketamine is a dissociative anesthetic medication that provides potent analgesia and is often used for procedural sedation. 60 Its mechanism of action is via antagonism of the NMDA receptor. Activation of NMDA receptors in the airways leads to release of sensory neuropeptides that activate smooth muscle contraction. ...
Pediatric critical asthma, or formerly known as status asthmaticus, is a common pediatric condition encountered in emergency departments, hospital wards, and pediatric intensive care units. Systemic corticosteroids and inhaled bronchodilators are evidence-based, initial treatments for patients with pediatric critical asthma. If clinical symptoms do not improve, pediatric practitioners often prescribe adjunctive medications including inhaled anticholinergics, intravenous ketamine, intravenous magnesium, intravenous short acting beta 2 agonists, and intravenous methylxanthines (such as aminophylline). In this narrative review, we will summarize the current evidence and present the research gaps related to these therapies in the pediatric population.
... Its onset of action is within 30 seconds of intravenous administration and it has a half-life of 2.5 hours [3]. Ketamine is metabolized by liver through N-demethylation and hydroxylation, which is in turn excreted into urine (90%) and bile (10%) [4]. This substance acts as an antagonist on N-methyl-D-aspartate (NMDA) receptors and noncompetitively blocks glutamate [5]. ...
Background and aims
Anesthesiologists prefer ketamine for certain surgeries due to its effectiveness as a non-competitive inhibitor of the N-methyl-D-aspartate receptor in the brain. Recently, this agent has also shown promise as an antidepressant. However, ketamine can cause hallucinogenic effects and is sometimes abused as an illicit drug. Ketamine abuse has been associated with liver and bile duct complications. This systematic study aims to better understand cholangiopathy in ketamine abusers by reviewing case reports.
Methods and material
In this systematic review, a comprehensive literature search was conducted with the terms “biliary tract diseases” and “ketamine”. Case reports and case series of adult patients with documented ketamine abuse and reported cholangiopathy or biliary tract disease were included. We extracted the data of relevant information and the results were reported through narrative synthesis and descriptive statistics.
Results
A total of 48 studies were initially identified, and 11 studies were finally included in the review. The mean age of the patients was 25.88 years. Of the 17 patients, 64.7% were men. Symptoms often included abdominal pain, nausea, and vomiting. Most patients were discharged with improved symptoms and liver function. Common bile duct dilation and other findings were observed in imaging results and other diagnostic studies.
Conclusion
This review highlights the diverse presentations and diagnostic modalities used in ketamine-induced cholangiography. These patients tend to be young men with deranged liver function tests and abdominal pain, which should be taken into consideration. These patients often require a multidisciplinary approach in their management.
... In the studies of Kolata and Rawlings, (1982) showed that combination of Ketamine+xylazine premedicated with atropine in dogs caused a rise in arterial pressure, left atrial pressure and peripheral resistance [34]. Ketamine has been shown to have analgesic properties which are attributable to direct antagonism of the N-methyl-D-aspartate receptors; stimulates cardiovascular system, it differs from most anesthetic agents it producing change in pressure of blood and it rises the concentration of catecholamine resulting rise in pressure of blood and cardiac output [35,36]. When atropine is premedicated with xylazine, it produced strong hypertension [37]. ...
CLINICAL anesthetic trial was conducted on 12 local dogs in different age, sexand body weight. The aim of study is to investigate the compatartive effectof ketamine and xylazine combination injected either IM or IV on the anetshetic(induction times, duration of anesthesia and recovery time) and physiologicalparameters on the dogs. They were divided into two groups (G-I and G-II) randomly.All dogs were administered with atropine sulphate (0.04mg\kg BW, IM) 5 minutesbefore anesthetic protocol, ketamine+xylazine (10mg\kg+1mg\kg) respectively, wasadminstered IM in G-I and IV in G-II. Clinical findings including inductions, durationand recovery period of anestehsia, HR, RR, RT, SPO2, SBP, DBP and MAP wererecorded before and during anesthesia. The study show that there were no significantdifferences between G-I and G-II in physiological parameters of ketamine andxylazine anethesia in dogs except induction, duration and recovery of anesthesia waslonger in G- I than G-II. In conclusion, the results demonstrated that the combinationof ketamine+xylazine can be a special satisfatcory anesthetic protocol for excellentinduction, good muscle relaxant and smooth recovery in dogs.Keyword: Ketamine, Xylazine, Intavenously, Intramuscularly, Dogs
(2) (PDF) Comparative Study Between IV and IM Co-administration of Xylazine with Ketamine on Some Physiological Parameters in Dogs. Available from: https://www.researchgate.net/publication/376117539_Comparative_Study_Between_IV_and_IM_Co-administration_of_Xylazine_with_Ketamine_on_Some_Physiological_Parameters_in_Dogs [accessed Feb 25 2024].
... A particular vulnerability of memory function in response to N 2 O inhalation can be expected when considering its pharmacological profile, that is, NMDAR antagonism and BDR agonism. Antagonists of the NMDAR, such as ketamine (Haas & Harper, 1992;Wolff & Winstock, 2006) and phencyclidine (Cosgrove & Newell, 1991;Wass et al., 2006), and BDR agonists (Lister, 1985;Mejo, 1992;O'Boyle, 1988) are known to induce profound anterograde amnesia. Also, activation of the NMDAR is believed to play a central role in the formation of long-term memories (Castellano et al., 2001;Collingridge & Bliss, 1987;Newcomer & Krystal, 2001;Nicoll & Malenka, 1999), which is conceivably attenuated by N 2 O induced NMDAR antagonism. ...
Nitrous oxide (N 2 O), colloquially known as laughing gas, is a common recreational drug of abuse. The gas is inhaled in its undiluted form from a party balloon. Its intoxicating effects are described as dissociative and euphoric, accompanied by ataxia, hypoxia, and attenuated consciousness. Therefore, the recreational use of N 2 O appears irreconcilable with operating a vehicle in road traffic. However, the Netherlands, one of the leading countries regarding prevalence of recreational N 2 O use, has seen a sharp increase in police reports of N 2 O‐related traffic incidents since 2016. Road traffic deaths associated with recreational N 2 O use have also been reported in the United Kingdom, as well as a recent increase in traffic incidents. Hence, driving under the influence of nitrous oxide (DUINO) is possibly an underreported threat to road traffic safety. Based on the limited information available at this time, the current review considers the prevalence of DUINO, its effects driving performance, and approaches to road‐side detection. It is concluded that DUINO is a potentially significant threat to road traffic safety. Although its prevalence is unclear, it is almost certain that DUINO is accompanied by severe driving impairment, based on its pharmacodynamics and documented cognitive and psychomotor effects in medical studies. The pharmacokinetic profile of N 2 O lends credibility to the notion that recent use can be demonstrated in breath, blood, and saliva. However, the analytical complexities of such measurements warrant elaborate research into N 2 O detection techniques.
This article is categorized under: Toxicology > Drug‐Impaired Driving
... Ketamine-induced dissociation can encompass a broad range of altered states that span the spectrum of aversive experiences, from relieving negative states to boosting positive feelings. Depersonalization and derealization involve disconnection from one's body and surroundings 9,10 . The ketamine-induced sensation of disconnecting from one's physical body may also be accompanied by detachment from negative affective and pain states, including emotional pain and depressive feelings 11 . ...
Ketamine commonly and rapidly induces dissociative and other altered states of consciousness (ASCs) in humans. However, the neural mechanisms that contribute to these experiences remain unknown. We used functional neuroimaging to engage key regions of the brain’s affective circuits during acute ketamine-induced ASCs within a randomized, multi-modal, placebo-controlled design examining placebo, 0.05 mg/kg ketamine, and 0.5 mg/kg ketamine in nonclinical adult participants (NCT03475277). Licensed clinicians monitored infusions for safety. Linear mixed effects models, analysis of variance, t-tests, and mediation models were used for statistical analyses. Our design enabled us to test our pre-specified primary and secondary endpoints, which were met: effects of ketamine across dose conditions on (1) emotional task-evoked brain activity, and (2) sub-components of dissociation and other ASCs. With this design, we also could disentangle which ketamine-induced affective brain states are dependent upon specific aspects of ASCs. Differently valenced ketamine-induced ASCs mediated opposing effects on right anterior insula activity. Participants experiencing relatively higher depersonalization induced by 0.5 mg/kg of ketamine showed relief from negative brain states (reduced task-evoked right anterior insula activity, 0.39 SD). In contrast, participants experiencing dissociative amnesia showed an exacerbation of insula activity (0.32 SD). These results in nonclinical participants may shed light on the mechanisms by which specific dissociative states predict response to ketamine in depressed individuals.
... Chronic pain/migraine Ketamine has been used for decades to treat chronic pain, particularly neuropathic pain, phantom limb pain, and fibromyalgia [127,128]. However, it remains unclear why ketamine is effective, or which forms of chronic pain it may target most effectively. ...
The discovery of ketamine as a rapid-acting antidepressant led to a new era in the development of neuropsychiatric therapeutics, one characterized by an antidepressant response that occurred within hours or days rather than weeks or months. Considerable clinical research supports the use of-or further research with-subanesthetic-dose ketamine and its (S)-enantiomer esketamine in multiple neuropsychiatric disorders including depression, bipolar disorder, anxiety spectrum disorders, substance use disorders, and eating disorders, as well as for the management of chronic pain. In addition, ketamine often effectively targets symptom domains associated with multiple disorders, such as anxiety, anhedonia, and suicidal ideation. This manuscript: 1) reviews the literature on the pharmacology and hypothesized mechanisms of subanesthetic-dose ketamine in clinical research; 2) describes similarities and differences in the mechanism of action and antidepressant efficacy between racemic ketamine, its (S) and (R) enantiomers, and its hydroxynorketamine (HNK) metabolite; 3) discusses the day-to-day use of ketamine in the clinical setting; 4) provides an overview of ketamine use in other psychiatric disorders and depression-related comorbidities (e.g., suicidal ideation); and 5) provides insights into the mechanisms of ketamine and therapeutic response gleaned from the study of other novel therapeutics and neuroimaging modalities.
... Ketamine is a short-acting general anesthetic with hallucinogenic, analgesic, and amnestic properties. It is used by medical practitioners and veterinarians as an analgesic and anesthetic (Haas and Harper, 1992;Laskowski et al., 2011;Sinner and Graf, 2008), but more recently was approved by the FDA for treatment of drug-resistant depression (Corriger and Pickering, 2019;Rosenblat et al., 2019). Due to its hallucinogenic and tranquilizer properties, ketamine is also abused by adolescents and young adults in rave, festival, or circuit party settings (Bates and Trujillo, 2021;Ross, 2008;Sassano-Higgins et al., 2016). ...
Ketamine is a short-acting general anesthetic with hallucinogenic, analgesic, and amnestic properties. In addition to its anesthetic use, ketamine is commonly abused in rave settings. While safe when used by medical professionals, uncontrolled recreational use of ketamine is dangerous, especially when mixed with other sedative drugs, including alcohol, benzodiazepines, and opioid drugs. Since synergistic antinociceptive interactions between opioids and ketamine were demonstrated in both preclinical and clinical studies, such an interaction could exist for the hypoxic effects of opioid drugs. Here, we focused on the basic physiological effects of ketamine as a recreational drug and its possible interactions with fentanyl-a highly potent opioid that induces strong respiratory depression and robust brain hypoxia. By using multi-site thermorecording in freely-moving rats, we showed that intravenous ketamine at a range of human relevant doses (3, 9, 27 mg/kg) dose-dependently increases locomotor activity and brain temperature, as assessed in the nucleus accumbens (NAc). By determining temperature differentials between the brain, temporal muscle, and skin, we showed that the brain hyperthermic effect of ketamine results from increased intracerebral heat production, an index of metabolic neural activation, and decreased heat loss due to peripheral vasoconstriction. By using oxygen sensors coupled with high-speed amperometry we showed that ketamine at the same doses increases NAc oxygen levels. Finally, co-administration of ketamine with intravenous fentanyl results in modest enhancement of fentanyl-induced brain hypoxia also enhancing the post-hypoxic oxygen increase. Therefore, in contrast to fentanyl, ketamine increases brain oxygenation but slightly potentiates brain hypoxia induced by fentanyl.
... Ketamin djeluju izravno ili neizravno na brojne transmitorske sustave. Primarno djeluje kao nekompetentivan potentan NMDA antagonist, inhibira djelovanje glutamata na receptore što ima za rezultat blokadu protoka kalcija kroz kanale (30,31). Na NMDA receptore, koji imaju važnu ulogu u neurokemiji ponašanja i procesiranju senzornih informacija, se veže na isto mjesto za koje se veže i PCP. ...
... The addition of ketamine to epidural lidocaine or bupivacaine increases the duration of regional anesthesia and post-operative analgesia. It has been seen that peri-incisional use of 0.3-0.5% ketamine combined with local anesthetic in surgical wounds enhances analgesia by a peripheral mechanism (11,12) . ...
... Ketamine is euphoric and dissociative in low doses, whereas at high doses it is immobilizing and hallucinogenic, with the incidence of emergence delirium being reported as high as 30% [3]. Ketamine is sold illicitly in pill, powder, and liquid forms and may be swallowed, drunk, smoked, sniffed, and injected intravenously or intramuscularly [4]. ...
A 33-year-old female presented with lethargy due to multidrug toxicity. At physical examination, both gluteal regions showed brown patchy scars. The atrophic scars surrounding necrotic lesions were round and brown in appearance, and gluteal mass had gradually been lost. The patient disclosed using intramuscular ketamine injections for 3.5 years along with smoking hashish, alcohol use, intranasal use of methamphetamine (sniffing), and oral use of methadone. Since recreational drug use can affect multiple organs, dermatologists should be familiar with the dermatologic features of intravenous or intramuscular injecting drug use.
... Ketamine was first synthesized in 1962 by the Parke Davis' organic chemist Calvin Stevens (Kolp et al., 2014). In its first human trials, clinicians found that at high doses, ketamine caused unconsciousness but at lower doses it produced peculiar psychoactive effects, with subjects describing being 'spaced out' and 'floating' (Domino et al., 1965(Domino et al., , 1984Haas and Harper, 1992). Importantly, this occurred in the middle of the 1960s, when classic psychedelics had started being used in poor controlled settings by the general population (Wolfson, 2014). ...
Ketamine is an N-methyl-d-aspartate antagonist which is increasingly being researched and used as a treatment for depression. In low doses, it can cause a transitory modification in consciousness which was classically labelled as ‘dissociation’. However, ketamine is also commonly classified as an atypical psychedelic and it has been recently reported that ego dissolution experiences during ketamine administration are associated with greater antidepressant response. Neuroimaging studies have highlighted several similarities between the effects of ketamine and those of serotonergic psychedelics in the brain; however, no unified account has been proposed for ketamine’s multi-level effects – from molecular to network and psychological levels. Here, we propose that the fast, albeit transient, antidepressant effects observed after ketamine infusions are mainly driven by its acute modulation of reward circuits and sub-acute increase in neuroplasticity, while its dissociative and psychedelic properties are driven by dose- and context-dependent disruption of large-scale functional networks. Computationally, as nodes of the salience network (SN) represent high-level priors about the body (‘minimal’ self) and nodes of the default-mode network (DMN) represent the highest-level priors about narrative self-experience (‘biographical’ self), we propose that transitory SN desegregation and disintegration accounts for ketamine’s ‘ dissociative’ state, while transitory DMN desegregation and disintegration accounts for ketamine’s ‘ psychedelic’ state. In psychedelic-assisted psychotherapy, a relaxation of the highest-level beliefs with psychotherapeutic support may allow a revision of pathological self-representation models, for which neuroplasticity plays a permissive role. Our account provides a multi-level rationale for using the psychedelic properties of ketamine to increase its long-term benefits.
... One of these drugs is the anesthetic ketamine (12-16). Ketamine's pharmacodynamic profile is that of a dissociative anesthetic and N-methyl-d-aspartate receptor (NMDA) receptor antagonist (17)(18)(19). Berman et al. was the first study to reveal that a single intravenous (IV) dose of ketamine as effective in treating MDD (20). Their randomized, doubl-blind study on a small group of subjects with MDD using IV ketamine hydrochloride (0.5 mg/kg) or saline over 2 days resulted in a significant reduction of depression symptoms as measured by a reduction in Hamilton Depression Rating Scale after ketamine treatment when compared to saline. ...
Intravenous and intranasal ketamine have been shown to be effective therapeutic options in patients suffering from treatment-resistant depression (TRD). The use of sublingual (SL), rapid dissolve ketamine tablets (RDT) offers a novel approach for delivery for mental health indications. This study assessed the effectiveness and safety of self-administration of off-label, SL, rapid dissolve ketamine tablets (RDT) at-home for depression and anxiety. Intake scores on the Generalized Anxiety Disorder Screener (GAD-7) and Patient Health Questionnaire (PHQ-9) were compared to scores after treatments of three doses of ketamine RDT, and after six doses of ketamine RDT. After three doses of SL ketamine, 47.6% of patients showed a significant decrease in PHQ-9 scores, and 47.6% of patients showed a significant reduction in GAD-7 scores. Reduction rates were higher in those patients who completed a clinically recommended six doses of RDT ketamine. This study demonstrates that SL ketamine is a novel, safe, and effective treatment for TRD and treatment-resistant anxiety. SL ketamine offers an alternative therapeutic approach to IV ketamine when treating those with TRD.
... Wydalana jest głównie z moczem, w niewielkim odsetku z kałem. Mimo że jest bardziej odpowiednia do stosowania podczas krótkich zabiegów, może być podawana w fazie podtrzymania w dawkach frakcjonowanych lub we wlewie ciągłym [17]. ...
In the past years, scientific reports present statements of a specific trend of an increase in dental caries among the children all over the world. This condition is influenced, among the others, by dietary habits, such as presence or overload of sugars in the diet and improper oral hygiene habits. The increase of tooth decay in children under the age of six, resulting in severe teeth decay, corresponds to frequency of general anesthesia in the treatment of pediatric patients. Dental treatment is one of the most common causes of medication intake in children. Moreover, general anesthesia enables timely and effective comprehensive care, which is a crucial condition, especially in reference to patients with special treatment needs.
The aim of the study
This work aims to raise awareness that the knowledge of types and doses of medications used by anesthesiologists during general anesthesia and its importance in order to achieve and maintain a high-quality standard for patients undergoing dental procedures under the general anesthesia.
Material and methods
The authors reviewed the novel publications, relating to the topic of medications (general anesthetics) most commonly used in general anesthesia during dental procedures in children.
Results
The publication presents important information on general anesthesia and the characteristics of individual groups of drugs, considering the specific and characteristic substances used by anesthesiologists.
Conclusion
In the opinion of the authors, the presented work is a kind of compendium of knowledge in the field of anesthesiology for the dentists performing procedures under general anesthesia in children, as well as for the dentists preparing to perform such procedures and for the doctors who receive patients with special dental care needs (such as mentally retarded patients), whose treatment is possible only under general anesthesia.
Key words: general anesthesia in children, anesthesiology, anesthetics, child dentistry
... The drug undergoes hepatic biotransformation by the liver into different metabolites, norketamine being the most important, a product of demethylation by the P450 cytochrome that is excreted by the kidneys (28). Readily distributed by the tissues, including the brain, ketamine is very lipid soluble and exhibits plasma protein binding (12%) with a half-life of around 10 min (29). Ketamine is an N-methyl D-aspartate (NMDA) receptor antagonist with additional weaker actions on sigma receptors, as well as noradrenalin, serotonin, and dopamine transporters among others (30,31). ...
Objective
Ketamine, an N-methyl D-aspartate (NMDA) receptor antagonist, can promote rapid action in the management of individuals with treatment-resistant depression (TRD) at sub-anesthetic doses. However, few studies have investigated the long-term use of ketamine administered intravenously (IV) and intranasally (IN). We report the design and rationale of a therapeutic trial for assessing the efficacy, safety, and tolerability of repeated-dose intramuscular (IM) ketamine vs. active treatment (escitalopram and aripiprazole) in TRD patients.
Methods
A comparative, parallel-group, randomized double-blind trial assessing the efficacy, safety, and tolerability of acute (4 weeks) and maintenance (24 weeks) use of IM ketamine (0.75 mg/kg) vs. active control (escitalopram 15 mg and aripiprazole 5 mg) in individuals with moderate-severe intensity TRD (no psychotic symptoms) with or without suicide risk will be conducted. Patients with TRD (18–40 years) will be randomized and blinded to receive ketamine IM or active treatment at a 1:1 ratio for 4 weeks (active treatment) and 24 weeks (maintenance treatment). Subjects will be assessed using clinical scales, monitored for vital signs (VS) after application of injectable medication, and undergo neuropsychological tests. The primary outcome will be changed on the Montgomery-Åsberg Depression Rating Scale (MADRS) during the course of the trial. The study is in running.
Results
This study can potentially yield evidence on the use of IM ketamine in the treatment of depressive disorders as an ultra-rapid low-cost therapy associated with less patient discomfort and reduced use of medical resources, and can elucidate long-term effects on different outcomes, such as neuropsychological aspects.
Conclusions
The trial can help promote the introduction of a novel accessible approach for the treatment of complex disease (TRD) and also allow refinement of its long-term use.
Clinical trial registration
https://clinicaltrials.gov/ct2/show/NCT04234776, identifier: NCT04234776.
... L'élimination de la kétamine se fait majoritairement par voie rénale. La kétamine et la norkétamine excrétées sous forme inchangée ne représentent que 2%, la déhydronorkétamine environ 16%(32,34,(47)(48)(49). Environ 80% de l'hydroxykétamine et l'hydroxynorketamine sont glucuronoconjuguées permettant une élimination biliaire et urinaire(34).Il semblerait que la demi-vie d'élimination de l'énantiomère S soit plus longue que le mélange racémique, de par la stéréosélectivité des cytochromes plus importante pour l'énantiomère R soit de l'ordre de 4 à 7 heures(18,28,30,50,51). ...
Ketamine was synthesized in the 60's derived from Phencyclidine (PCP) and being the leader of the arylcyclohexylamines. This molecule was widely used in anesthesia. It has the advantage of having a rapid and short-lived action, while impacting the respiratory functions. However, its use was greatly impacted by its psychotic and dissociative effects, and by the arrival on the market of other anesthetics such as Propofol in the 1980s. However, it is still widely used in veterinary anesthesia. A lot of studies have focused on other indications, revealing an interest in chronic pain and depression resistant to the usual chemotherapies. Although it has fallen into disuse in a therapeutic context, ketamine is a well-known recreational product. Its dissociative effects were initially only of interest to fringe groups, in free parties and the techno-alternative milieu, but its use is becoming more and more widespread. The recreational use of ketamine has clearly increased in the 2000s, especially thanks to facilitated logistical means such as the Dark Web. In the 2010s, and with the arrival of New Synthetic Products (NPS), new arylcyclohexylamine derivatives (NADs) have appeared on the Internet. Few cases have been described for the moment, even if some outbreaks seem to be important, especially in Asia. Their expansion seems to be cosmopolitan and exponential. Cases of intoxication have recently been imported into Europe and France. The detection of its new synthetic derivatives seems to be a major challenge for Toxicology laboratories.
... 28 Ketamine, an anesthetic agent, provides powerful analgesia and amnesia. 20 Ketamine efficacy has been reported in patients with refractory chronic pain at subanesthetic doses 4 and in phantom limb pain, 35 postherpetic neuropathic pain, 16 and CRPS. 33,34 Ketamine is commonly used in pain clinics for the management of chronic pain, but the efficacy of ketamine remains controversial in the literature on the short term, 12,32 and no study has followed patients beyond 3 months. ...
Background:
There is no recommendation in Europe for the use of ketamine in patients with chronic pain. The heterogeneity of practice highlights the need to seek the advice of experts in order to establish a national consensus. This Delphi survey aimed to reach a national consensus on the use of ketamine in chronic pain in Pain clinics.
Methods:
A collaborative four-round internet-based questionnaire was used. It was created after literature search on ketamine administration in chronic pain and included about 96 items. It discussed utility and advantages, adverse events and deleterious aspects, methods of administration, concomitant treatments and assessment of results.
Results:
Twenty-eight experts completed all rounds of the survey with a total of 81.3% items reaching a consensual answer. Neuropathic pain represents the first indication to use ketamine, followed, with a good to moderate utility, by other situations (fibromyalgia, complex regional pain syndrome, central neuropathic pain, peripheral neuropathic pain, nociceptive pain, sensitization, opioid withdrawal, palliative care, depression). Experts agreed on the rare occurrence of adverse events. Concerning routes of administration, intravenous infusion with doses of 0.5-0.9mg/kg/d for four days of treatment is preferred. Place of care is hospital, as in- or out-patient, with a quarterly administration of ketamine. Finally, ketamine effectiveness is assessed one month after infusion, and experts encourage combination with non-pharmacological treatment.
Conclusions:
This Delphi survey established a consensus of pain specialists on the use of ketamine in refractory chronic pain, thus providing a basis for future comparative trials.
Significance:
This Delphi survey in chronic pain reached agreement on 4 main aspects: 1) Priority to treat neuropathic pain with evaluation of effectiveness at 1 month; 2) No deleterious effects in the majority of listed diseases/situations with the absence or < 3% of suggested adverse events; 3) 0.5-0.9mg/kg/d IV infusion; 4) Combination with non-pharmacological treatment.
... Ketamine is an anesthetic agent, also used for the treatment of depression. It differs from other anesthetic agents as it stimulates the cardiovascular system, thus affecting the heart rate, cardiac output, blood pressure, and a slight rise in intracranial pressure (40,41). Along with the western world, ketamine is widely used in Asian countries, specifically Hong Kong where it is called 'Club Drug', China, Indonesia, Brunei Darussalam and Malaysia (42,43). ...
... Ketamine metabolizes rapidly within minutes and is distributed quickly in highly perfused tissues. The rapid transfer of ketamine across the blood-brain-barrier into the brain is facilitated by its liposolubility and low plasma protein binding properties (Haas and Harper, 1992). Structurally, ketamine is a racemic mixture of R-and S-ketamine and the effect of ketamine is suggested to be through the function of its active metabolites most notably hydroxynorketamines. ...
Major depressive disorder (MDD) is a common psychiatric disorder with multifactorial aetiology and complex pathophysiology. Despite availability of various pharmacological and non-pharmacological therapeutic strategies, treatment resistant depression (TRD) remains a significant challenge with specific concern for those patients with severe depressive symptoms in particular suicidal ideations who require immediate and effective intervention. Inflammation has been widely studied for its association with MDD and treatment response. Ketamine known as a dissociative anaesthetic has a novel rapid-acting antidepressant effect at lower doses. Anti-inflammatory actions of ketamine appear to play a role in mechanisms underlying its antidepressant effects. Considering the rapid antidepressant action of ketamine, this review provides a brief overview of antidepressant properties of ketamine as well as its effects on peripheral and central inflammation to better understand the mechanisms underlying the therapeutic action of ketamine as an anti-inflammatory antidepressant target in psychiatric emergency. Development of effective medications, which act rapidly with dual effect on both inflammation and MDD would be of a significant clinical importance for a successful and personalised treatment of inflammatory-induced TRD and suicidal thoughts and behaviour.
... One of the key acute experiences that ketamine induces is dissociation, which is broadly defined as feelings of disconnection from one's body and/or environment. In the context of ketamine, it may include a general sensory detachment, mind-body uncoupling, and feelings of floating in the absence of delirium [3,4]. While challenging to obtain estimates of the prevalence of dissociation in abuse settings, this effect is known to commonly occur at doses therapeutic for TRD. ...
Ketamine is a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptor that is both a drug of abuse and an FDA-approved anesthetic used off-label for treatment-resistant depression. Despite its growing clinical use for depression and pain, the relationships between the acute dissociative and affective effects of ketamine that contribute to its abuse liability and therapeutic potential, along with the neural mechanisms underlying these effects, are not well established. To address this need, we have implemented a randomized, double-blinded, placebo-controlled, within-subjects mechanistic trial. Healthy adult subjects undergo infusion with two fixed doses of subanesthetic racemic intravenous (IV) ketamine and placebo and their acute responses are assessed with self-report questionnaires, behavioral measures, hormone levels, and neuroimaging. As planned in our analysis strategy, we present interim results for the first 7 subjects of our study, focusing on dissociative and affective states and resting functional brain coupling signatures of these states. The first key finding was that ketamine induced dose-dependent increases in dissociation and related intoxication. Ketamine also altered affective states, reducing emotional insensitivity but increasing stress assessed by cortisol. Second, ketamine had an effect on altering brain connectivity, particularly for specific connections between regions of the reward and negative affect circuits and involving thalamic sub-regions. Third, regarding brain-response associations, ketamine-induced increases in amygdala-anteroventral thalamus coupling were correlated with greater dissociation and intoxication, whereas decreases in the coupling of the anteromedial thalamus and posterior parietal thalamus were correlated with increased sensory aspects of reward responsiveness. Additional specific correlations were observed between affective measures relevant to reward responsiveness or its absence and drug-altered changes in localized functional connections involving the nucleus accumbens (NAcc), amygdala, and thalamic sub-regions. We also discovered a consistent profile of negative associations between ketamine altered connectivity involving the NAcc and specific thalamic sub-regions and effects of anxiety. Further, drug-altered increases in the coupling of the amygdala and anteroventral thalamus were associated with increases in cortisol, an indicator of biochemical stress. The findings highlight the utility of integrating self-reports, objective measures, and functional neuroimaging to disentangle the brain states underlying specific acute responses induced by ketamine. With the likely continued expansion of FDA indications for ketamine, understanding acute responses and underlying neural mechanisms is important for maximizing the therapeutic potential of ketamine while minimizing the risk of promoting misuse or abuse of this substance. Clinical Trial Registration ID #: NCT03475277
... As part of this effort, ketamine was discovered in 1965, and despite its similar chemical structure to phencyclidine, initial studies suggested that it had fewer adverse effects in humans, providing safe and effective sedation, analgesia and amnesia (Harari and Netzer 1994;Jansen 2004). Its action is mainly explained by acting as a potent antagonist to N-methyl-D-aspartate (NMDA) glutamate receptors (Haas and Harper 1992), reducing the excitability of the central nervous system. Ketamine is currently used as a dissociative anesthetic mainly in veterinary medicine although it can also be used in clinics and is approved by regulatory agencies in several countries around the world. ...
... As part of this effort, ketamine was discovered in 1965, and despite its similar chemical structure to phencyclidine, initial studies suggested that it had fewer adverse effects in humans, providing safe and effective sedation, analgesia and amnesia (Harari and Netzer 1994;Jansen 2004). Its action is mainly explained by acting as a potent antagonist to N-methyl-D-aspartate (NMDA) glutamate receptors (Haas and Harper 1992), reducing the excitability of the central nervous system. Ketamine is currently used as a dissociative anesthetic mainly in veterinary medicine although it can also be used in clinics and is approved by regulatory agencies in several countries around the world. ...
Research carried out in the 1950s and 1960s highlighted the therapeutic potential of some hallucinogens for various clinical conditions, but the inclusion of these substances on the Schedule I in the United Nations Convention on Psychotropic Substances made access to them difficult and studies of such drugs dropped dramatically in the following decades. However, there has been a growing resurgence of interest in hallucinogens and several clinical studies have been conducted to evaluate the effectiveness of hallucinogens in mood disorders (depression and anxiety, including treatment-resistant depression), post-traumatic stress disorder, chronic pain, drug addiction and to improve the mood and psychological condition of patients suffering from terminal or life-threatening diseases. Among the most studied substances with the strongest evidence of efficacy and safety, within defined dosages and conditions, are LSD, DMT, ketamine, and psilocybin. Such substances have shown promising for the treatment of psychiatric conditions such as mood disorders and drug addiction, when used under controlled conditions and under medical supervision. This chapter addresses the main hallucinogens used therapeutically for the treatment of neurological and psychiatric conditions.
... e safety and effectiveness of ketamine to sedate prehospital and emergency department (ED) patients with undifferentiated agitation have been reported in a systematic review and meta-analysis [13]. Likewise, there have been several reports on ketamine use in clinical procedures and trials among children and adolescents in developed countries [11,[14][15][16][17][18][19][20]. ...
Background:
Pain, anxiety, and distress are common in radiological investigations including hysterosalpingogram (HSG). Studies suggest that sedation allows patients to better tolerate diagnostic imaging and image-guided procedures by relieving anxiety, discomfort, and pain. This study aimed at assessing the safety and effectiveness of ketamine use in HSG and the proportion of true positive bilateral tubal blockage during HSG using the Jimah Procedure.
Methods:
We performed repeated HSG workup under IV ketamine (20-40 mg/mL) sedation for 27 infertile women at the Cape Coast Teaching Hospital. The exclusion criteria included unilateral tubular blockage, acute infection of the vagina or cervix, active vaginal bleeding, glaucoma, and high blood pressure at the time of the study. Data were entered with Microsoft Excel and analyzed using SPSS version 21.
Results:
A total of 27 patients (age range: 25-48 years) previously diagnosed of bilateral tubal blockage or spasm were enrolled for the repeat HSG procedure. The median age was 34 years (IQR: 32-37), while secondary infertility (20) (74.1%) was the commonest indication. None of the patients reported of pain or distress during or after the procedure. Two (7.4%) women vomited after HSG. Twelve patients (44.4%) had bilateral tubal blockage (true positive), while tubal patency was seen in 15 (55.6%) patients on HSG under ketamine sedation.
Conclusion:
This study found IV ketamine sedation produces profound anesthesia and analgesia and eliminates tubal spasm. We recommend that radiologists in developing countries should consider sedating patients during HSG and documenting observations and patients' feedback to help assess safety and effectiveness in local settings.
... Ketamine induces sympathomimetic cardiovascular and respiratory effects such as increased heart rate and blood pressure as well as bronchodilation with evidence for direct interaction of ketamine with alpha-1 and beta-2-adrenoceptors of the autonomous nervous system (Bevan et al., 1997). The dissociative syndrome at higher ketamine dosage refers to a functional and electrophysiological separation of contradictory nervous system activity (Haas and Harper, 1992) and is defined by a decrease of central nervous system (CNS) arousal, whereas the activity of the autonomous nervous system (ANS) is kept at high levels or even increases. When trying to figure out the mode of function of ketamine in MDD, one has to bear in mind that MDD has been associated with a hyperarousal by means of EEG wakefulness regulation (Hegerl et al., 2011; or sleep latency (Rotenberg et al., 2002). ...
Objective
Ketamine has been shown to be effective in treatment of episodes of major depressive disorder (MDD). This controlled study aimed to analyse the predictive and discriminative power of heart rate (HR) and heart rate variability (HRV) for ketamine treatment in MDD.
Methods
In 51 patients, HR and HRV were assessed at baseline before and during ketamine infusion and 24 hours post ketamine infusion. Montgomery–Åsberg Depression Rating Scale (MADRS) was used to assess changes of depressive symptoms. A 30% or 50% reduction of symptoms after 24 hours or within 7 days was defined as response. A linear mixed model was used for analysis.
Results
Ketamine infusion increased HR and HRV power during and after infusion. Responders to ketamine showed a higher HR during the whole course of investigation, including at baseline with medium effect sizes (Cohen‘s d=0.47-0.67). Furthermore, HR and HRV power discriminated between responders and non-responders, while normalized low and high frequencies did not.
Conclusion
The findings show a predictive value of HR and HRV power for ketamine treatment. This further underlines the importance of the autonomous nervous system (ANS) and its possible malfunctions in MDD.
Significance
The predictive power of HR and HRV markers should be studied in prospective studies. Neurophysiological markers could improve treatment for MDD via optimizing the choice of treatments.
... Dexmedetomidine has been successfully used in brachial plexus block [11]. Ketamine is a noncompetitive blocker of the N-methyl-D aspartate (NMDA) receptor it is used for premedication, sedation, induction, and maintenance of general anesthesia [12]. It has shown that adding ketamine to epidural bupivacaine or lidocaine could increase the duration of regional anesthesia and postoperative analgesia [13]. ...
Background: Peripheral nerve block has gained increased popularity due to less postoperative pain, reduced need for postoperative analgesic drugs, reduction of PACU time, and improved patient satisfaction. The aim of the study was to compare the effect of ketamine and dexmedetomidine as additives to bupivacaine on onset and duration of the block, post-operative VAS, and analgesic consumption, after ultrasound-guided supraclavicular nerve block.
Methods: 75 adult patients undergoing elective operations of the elbow, forearm, wrist, or hand were randomly allocated into three groups of 25 patients each. Group K (ketamine group) received 40 ml 0.25% bupivacaine contain 1 mg/kg ketamine, Group D (dexmedetomidine group) received 40 ml 0.25% bupivacaine contain 1ug/kg dexmedetomidine, group C (control group) received 40 ml 0.25% bupivacaine. The outcome measures included visual analog scale (VAS, 0 = no pain 10 cm = the most severe pain), time to first analgesic request, and total dose of diclofenac analgesia given postoperatively. Sedation score also recorded in all groups
Results: Patients in D and K groups had reduced VAS scores than the C group, at all-time points after surgery during the first 24 hours, with more reduction in D than K group ( P < 0.05). The time of the first analgesic request in the D group was significantly more than in the K group and both were more than the C group (9.48±1.417 h, 7.08 ±1.255 h, and 5.00 ± 1.04 h respectively).
Conclusions: The addition of ketamine or dexmedetomidine in the ultrasound-guided supraclavicular brachial plexus block could improve the postoperative pain and need for analgesia. Therefore, we can consider the low price more available ketamine as a comparable adjuvant in brachial plexus block to some extent as dexmedetomidine.
Trial registration: https://www.clinicaltrials.gov/ct2/show/NCT04508894, Date of registration (02/21/2019).
... The rate of elimination of ketamine is twice as rapid in children when compared to adults, likely due to faster enzymatic metabolism in children. 29 This information plays a role in determining the ketamine dosing frequency in children. Ketamine is commonly available as a mixture of (S)-and (R)-enantiomers. ...
Ketamine is a dissociative anesthetic agent with excellent analgesic properties and a favorable safety profile. The feasibility and efficacy of various routes of administration have been established, including intravenous (IV), intramuscular (IM), oral, intranasal, rectal, and transdermal routes. The advent of newer anesthetic agents has led to a decline in the use of ketamine as an anesthetic, but its utility in short‐term sedation and analgesia has expanded. Its value for chronic pain management in children with cancer is being increasingly recognized but requires more evidence. The use of topical ketamine is largely in investigational stages. Medical use of ketamine is, to a great extent, free from significant long‐term neurological side effects. The objective of this review is to provide a brief account of the pharmacology of ketamine and primarily focus on the clinical applications of ketamine in pediatric oncology.
... The rate of elimination of ketamine is twice as rapid in children when compared to adults, likely due to faster enzymatic metabolism in children. 29 This information plays a role in determining the ketamine dosing frequency in children. Ketamine is commonly available as a mixture of (S)-and (R)-enantiomers. ...
The administration of intravenous agents is the most used method in Canada and the United for the purpose of producing general anesthesia or sedation for dental procedures. Some of the pharmacokinetic, pharmacodynamic, and physical characteristics of ketamine, a dissociative anesthetic, are favorable. It can cause amnesia, sedation, analgesia, and anesthesia. Ketamine can maintain functional residual capacity, induce bronchodilation, and avoid cardiovascular depression. However, adverse effects have been demonstrated, such as cardiovascular stimulation and unpleasant emergence phenomena, both of which may be modulated by supplementation with benzodiazepines. An increase in the Ketamine has lately been promoted for use in ambulatory anesthesia. The use of ketamine as an effective agent for specific anesthetic procedures is supported by this review of the literature
There are global concerns about the proliferation and misuse of club drugs and novel psychoactive substances, yet we know little about their harms and research on clinical management and treatment remains limited. This book fills the knowledge gap by providing a detailed overview of the research evidence available to date. The book provides a framework that allows readers to understand this large number of new drugs, using classifications based on primary psychoactive effect. Within this framework, the book provides detailed reviews of the more commonly used drugs. Each chapter explores pharmacology, patterns and mode of use, acute and chronic harms, and clinical interventions supported by research evidence. An invaluable resource for clinical staff, this book will support clinicians working in the emergency department, substance misuse and addiction services, mental health services, primary care, sexual health services and more. It will also be of interest to academics and those developing drug policy.
Background
Major Depression is the leading cause of disability worldwide. A cohort of patients do not respond adequately to available antidepressants, leading to treatment-resistant depression (TRD). We evaluated the antidepressant efficacy of an acute intravenous ketamine treatment (0.5 mg/kg) for patients with unipolar TRD, and measured peripheral blood-based biomarkers associated with response to treatment.
Methods
Fifteen adults diagnosed with TRD completed an open label study of ten infusions of subanesthetic ketamine over four weeks. Out of fifteen patients, blood was collected from eleven patients at three timepoints to analyze peripheral biomarkers in isolated plasma, including IL-6, IL-10, TNF-α, BDNF, and irisin. Irisin analysis was completed using an ELISA assay, and the remaining biomarkers were analyzed together simultaneously using a multiplex immunoassay.
Results
Repeated ketamine infusions produced a significant decrease in total average depressive symptoms (MADRS) at all timepoints. Improvements in depressive symptoms were significant at one week, and continued to significantly decrease until two weeks, where it was maintained. Ketamine was generally well tolerated, and we observed improvements in functional impairment, anhedonia, and psychiatric symptoms, with no increases in manic symptoms. Levels of BDNF throughout treatment inversely correlated to decreases in MADRS scores, and higher levels of baseline BDNF predicted mood responses at one- and four weeks.
Limitations
The study was observational and uncontrolled, with a sample size of 15. Outpatients remained on their course of medications, unless they were pharmacological agents that have previously been identified to block ketamine's effects.
Conclusions
Ketamine may be an efficacious and safe pharmacological option for the acute treatment of patients suffering from severe TRD. BDNF has the potential to function as a prognostic biomarker for predicting response to ketamine treatments.
Background
Anesthesia and psychotropic drugs in pregnant women may cause long-term effects on the brain development of unborn babies. The authors set out to investigate the neurotoxicity of S-ketamine, which possesses anesthetic and antidepressant effects and may cause attention deficit hyperactivity disorder (ADHD)- and depression-like behaviors in offspring mice.
Methods
Pregnant mice were administered with low-, medium-, and high-dose S-ketamine (15, 30, and 60 mg/kg) by intraperitoneal injection for 5 days from gestational day 14 to 18. At 21 days after birth, an elevated plus-maze test, fear conditioning, open field test, and forced swimming test were used to assess ADHD- and depression-like behaviors. Neuronal amount, glial activation, synaptic function indicated by ki67, and inhibitory presynaptic proteins revealed by GAD2 in the hippocampus, amygdala, habenula nucleus, and lateral hypothalamus (LHA) were determined by immunofluorescence assay.
Results
All the pregnant mice exposed to high-dose S-ketamine administration had miscarriage after the first injection. Both low-dose and medium-dose S-ketamine administration significantly increased the open-arm time and attenuated frozen time in the fear conditioning, which indicates impulsivity and memory dysfunction-like behaviors. Medium-dose S-ketamine administration reduced locomotor activity in the open field and increased immobility time in the forced swimming test, indicating depression-like behaviors. Changes in astrocytic activation, synaptic dysfunction, and decreased inhibitory presynaptic proteins were found in the hippocampus, amygdala, and habenula nucleus.
Conclusions
These results demonstrate that S-ketamine may lead to detrimental effects, including ADHD-and depression-like behaviors in offspring mice. More studies should be promoted to determine the neurotoxicity of S-ketamine in the developing brain.
Background:
Pecs-II block has previously and successfully demonstrated a good quality of perioperative analgesia for breast surgery.
Objective:
This study aimed to compare the quality of postoperative pain control when adding either ketamine or dexmedetomidine to bupivacaine 0.25% for Pecs-II block.
Methods:
This prospective randomized double-blind study was conducted on 159 female patients with American society of anesthesiologist (ASA) physical status class I-III scheduled to have modified radical mastectomy. Patients were randomly assigned into three groups. Each group included 53patients to receive ultrasound guided Pecs-II blocks with either 32 mL of 0.25% bupivacaine added to ketamine hydrochloride 1 mg/kg (BK group), 32 mL of 0.25%bupivacaine added to dexmedetomidine 1 ug/kg (BD group) or 32 mL of 0.25% bupivacaine only (B group).The primary outcome of this study was the total postoperative morphine consumption for the first 24 hours postoperatively. The time of the first request of analgesia, the pain scores at rest of ipsilateral arm, and the intra-operative fentanyl requirements, were the secondary outcome measures. Any side effects occurred were recorded.
Results:
The total postoperative morphine consumption was significantly lower in patients received bupivacaine with addition of either ketamine (BK group), (10.3±2.6 mg), or dexmedetomidine (BD group), (3.8±0.2 mg) respectively, versus patients received only bupivacaine (B group), (16.9±5.3 mg). Both ketamine (BK group) and dexmedetomidine (BD group) added to bupivacaine significantly prolonged the time to first analgesic request (16.7±4.5 h), (21.6±1.6 h) in both groups respectively compared to patients received bupivacaine alone (B group), (11.5±1.2 h).The pain score was variable between the three groups over different times during the first 24 hours postoperatively. There was no significant difference in perioperative hemodynamics, O2 saturation, sedation scores or side effects observed between the three groups. Patient satisfaction was reported to be the best in patients received dexmedetomidine added to bupivacaine than the other patients who received ketamine as an additive or those who received bupivacaine alone.
Conclusion:
Adding dexmedetomidine to bupivacaine provides more effective postoperative pain control than adding ketamine during Pecs-II blocks for breast cancer surgery.
Perioperative neurocognitive disorder (PND) is a common complication associated with anesthesia and surgery in the elderly. The dysfunction of transient receptor potential vanilloid 4 (TRPV4) has been associated with a number of diseases, including Alzheimer's disease. Given that ketamine can reportedly improve PNDs, the present study sought to determine whether ketamine-induced PND alleviation was mediated by activation of TRPV4 channel opening. A total of 120, 20-month-old male C57BL/6 mice were randomly divided into five groups: Vehicle, PND (tibial fracture surgery), PND + ketamine (Ket), PND + Ket + HC-067047 (HC), and PND + HC groups. Ketamine (0.5 mg/kg) was administered intraperitoneally once a day for 3 days after surgery and HC-067047 (1 µmol/2 µl), an antagonist of TRPV4, was administered via the left lateral ventricle 30 min before ketamine treatment. Superoxide dismutase (SOD), malondialdehyde (MDA), lipid peroxidation (LPO), IL-1β, IL-6, adenosine monophosphate-activated protein kinase (AMPK), NF-κB, TNF-α and IFN-β levels were determined 3 days after surgery. At 28 days after surgery, fear conditioning and novel object recognition were assessed, and Aβ1-42 levels were measured and ionized calcium binding adaptor molecule 1 (Iba1) staining was conducted on day 31 after surgery. The results revealed that ketamine administration upregulated total SOD activity, downregulated MDA and LPO content, mitigated phosphorylated (p)-NF-κB, TNF-α mRNA and IFN-β mRNA expression in the hippocampus, and promoted p-AMPK 3 days after surgery. Furthermore, it was found that ketamine increased both context- and tone-dependent fear conditioning, and the time spent exploring a novel object, and reduced Aβ peptide levels and microglial activation 30 days after surgery. Notably, these changes could be reversed by HC-067047 to a certain extent. In conclusion, ketamine improved PND in aged mice after tibial fracture surgery and the potential mechanism may involve activation of the TRPV4/AMPK/NF-κB signaling pathway.
Keeping abreast with current literature can be challenging, especially for practitioners caring for patients sustaining thermal or inhalation injury. Practitioners caring for patients with thermal injuries publish in a wide variety of journals, which further increases the complexity for those with resource limitations. Pharmacotherapy research continues to be a minority focus in primary literature. This review is a renewal of previous years’ work to facilitate extraction and review of the most recent pharmacotherapy-centric studies in patients with thermal and inhalation injury. Sixteen geographically dispersed, board-certified pharmacists participated in the review. A MeSH-based, filtered search returned 1,536 manuscripts over the previous 2-year period. After manual review and exclusions, only 98 (6.4%) manuscripts were determined to have a potential impact on current pharmacotherapy practices and included in the review. A summary of the 10 articles that scored highest are included in the review. Nearly half of the reviewed manuscripts were assessed to lack a significant impact on current practice. Despite an increase in published literature over the previous 2-year review, the focus and quality remain unchanged. There remains a need for investment in well-designed, high impact, pharmacotherapy-pertinent research for patients sustaining thermal or inhalation injuries.
Ketamine is a dissociative anesthetic with proconvulsant properties that acts by noncompetitively blocking the N-methyl-d-aspartate receptors (NMDARs) in the central nervous system (CNS). In general, scalp electroencephalography (EEG) demonstrates low amplitude paroxysmal fast activity (PFA) at low doses, associated with mild sedation, and slow waves as well as burst suppression (BS) pattern associated with unconsciousness at higher doses. Intracranial EEG studies support initial changes of burst suppression pattern occurring in the parieto-occipital regions before frontal propagation suggesting that initial anesthetic effects are associated with activation in the posterior hemispheres, especially the occipital lobes. Initially in people predisposed to epilepsy, ketamine may lower seizure thresholds and increase interictal epileptiform discharges (IEDs) within minutes of administration. In this chapter, we will discuss EEG changes encountered with ketamine administration and compare its anesthetic and proconvulsant effects on EEG with other anesthetics.
This article focuses on sedation/anesthesia of adolescent patients in the dental setting. Preoperative evaluation, treatment planning, monitoring, and management are critical components to successful sedation. The authors discuss commonly administered agents and techniques to adolescents, including nitrous oxide/oxygen analgesia. The levels and spectrum of sedation and anesthesia are reviewed. Common comorbidities are also presented as they relate to sedation of the adolescent dental patient.
Ketamine is often used in pain clinics for refractory chronic pain, but its long-term efficacy is poorly reported. The main objective was to assess the long-term effect of ketamine on pain and health variables in patients with refractory chronic pain.A prospective, multicenter, one-year follow-up observational study (NCT03319238) was conducted in thirty French pain clinics where ketamine is commonly prescribed. This study focused on patients with one ketamine delivery procedure (n=256). The primary endpoint was pain intensity (0-10 numerical pain rating scale) before and after ketamine every month for one year. Secondary outcomes aimed to identify pain trajectories by semi-parametric mixture models and to collect adverse events.The following data were obtained for 256 patients: pain intensity decreased significantly (6.8±1.8, n=240 at baseline versus 5.7±1.8, n=93 at 12 months, p<0.001). The effect size of the main endpoint was 0.61 (95%CI: [0.40; 0.80]; p<0.001). Three pain trajectories were identified: 16.0% of patients in "mild pain" (mostly neuropathic pain), 35.3% in "moderate pain" and 45.7% in "severe pain" (mostly fibromyalgia) trajectory. Neuropathic pain and fibromyalgia presented opposite outcomes, pain severity being associated with anxiety, depression and a poorer quality of life. Adverse events occurred at one week in 108/218 [50%] patients and this rate gradually decreased throughout the follow-up.This real-life study in chronic pain identified distinct pain trajectories and predictive variables of ketamine efficacy. It is now pivotal to further study and optimize the subtyping of patients to provide the most effective and safe ketamine treatment in this vulnerable population.
Bronchiolitis obliterans is rarely described in the nonlung transplant anesthesia literature. This case report describes a 27-year-old female patient with idiopathic bronchiolitis obliterans and dental anxiety who safely received intravenous deep sedation using diphenhydramine, dexmedetomidine, and ketamine in an ambulatory community dental clinic. This report outlines the anesthetic plan developed following a thorough preoperative assessment and review of the key anesthetic considerations of idiopathic bronchiolitis obliterans (eg, potential respiratory complications and appropriateness for the ambulatory dental environment) and discusses the careful anesthetic management of this patient using deep sedation to facilitate comprehensive restorative dentistry.
Introduction:
Perioperative use of ketamine has been discussed widely in many kinds of surgery. The aim of our study was to evaluate the short-term and long-term benefits and safety of ketamine after breast surgery.
Method:
We performed a quantitative systematic review. We included randomized controlled trials that compared intravenous administration of ketamine to a placebo control group, or compared bupivacaine in combination with ketamine to bupivacaine alone in thoracic paravertebral blocks or pectoral blocks among patients undergoing breast surgery. The primary outcome was postoperative pain intensity. Secondary outcomes included cumulative opioid consumption during the 0- to 24-hour postoperative period, the effect on postmastectomy pain syndrome, the effect on postoperative depression, and the adverse events associated with the use of ketamine.
Results:
Thirteen randomized controlled trials with 1,182 patients were included for analysis. Compared with placebo, intravenous ketamine was effective in reducing wound pain intensity during the first 6 hours after surgery (weighted mean difference [WMD] -0.83; 95% confidence interval [CI] -1.65, -0.01; P = 0.048) and during the first 24 hours after surgery (WMD -0.65; 95% CI -0.95, -0.35; P < 0.001), and in decreasing opioid consumption (WMD -4.14; 95% CI -8.00, -0.29; P = 0.035) during the first 24 hours after surgery, without increasing the risks for gastrointestinal and central nervous system adverse events. Adding ketamine to bupivacaine in thoracic paravertebral blocks was also effective in reducing postoperative wound pain during the first 6 hours after surgery (WMD -0.59; 95% CI, -1.06, -0.12; P = 0.014) and during the first 24 hours after surgery (WMD -0.90; 95% CI -1.27, -0.53; P < 0.001), and in decreasing opioid consumption (WMD - 4.59; 95% CI -5.76, -3.42; P < 0.001) during the first 24 hours after surgery. Perioperative use of ketamine was associated with improved postoperative depression symptoms (standardized mean difference -0.80; 95% CI - 1.34, -0.27; P = 0.003) and less incidence of postmastectomy pain syndrome (relative risk 0.79; 95% CI 0.63, 0.99; P = 0.043).
Conclusion:
Ketamine is an effective and safe multimodal analgesic in patients undergoing breast surgery, administered both intravenously and when added to bupivacaine in paravertebral blocks. In addition, ketamine showed a long-term benefit for preventing postoperative depression and postmastectomy pain syndrome.
Background
Ketamine produces significant rapid-onset and robust antidepressant effects in patients with major depressive disorder. However, this drug also has transient cardiovascular stimulatory effects, and there are limited data about potential predictors of these cardiovascular effects.
Methods
A total of 135 patients with unipolar and bipolar depression received a total of 741 ketamine infusions (0.5 mg/kg over 40 min). Blood pressure and pulse were monitored every 10 min during the infusions and 30 min after the infusions. Depressive, psychotomimetic and dissociative symptom severity was assessed at baseline and 4 hours after each infusion.
Results
The maximum blood pressure and pulse values were observed at 30–40 min during infusions. The largest mean systolic/diastolic blood pressure increases were 7.4/6.0 mmHg, and the largest mean pulse increase was 1.9 beats per min. No significant change in blood pressure and pulse was found in the second to sixth infusions compared with the first infusion. Patients who were older (age⩾50 years), hypertensive and receiving infusions while exhibiting dissociative symptoms showed greater maximal changes in systolic and diastolic blood pressure than patients who were younger (age<50 years), normotensive and without dissociative symptoms (all p < 0.05). Hypertensive patients had less elevation of pulse than normotensive patients ( p < 0.05). Ketamine dosage was positively correlated with changes in systolic and diastolic blood pressure (all p < 0.05).
Conclusions
Blood pressure and pulse elevations following subanaesthetic ketamine infusions are transient and do not cause serious cardiovascular events. Older age, hypertension, large ketamine dosage and dissociative symptoms may predict increased ketamine-induced cardiovascular effects.
In nearly 25 years of clinical experience, the benefits and limitations of ketamine analgesia and anaesthesia have generally been well-defined. The extensive review of White et al. and the cardiovascular review of Reves et al. are broad in their scope and have advanced the understanding of dissociative anaesthesia. Nevertheless, recent research continues to illuminate different aspects of ketamine pharmacology, and suggests new clinical uses for this drug. The identification of the N-methylaspartate receptor gives further support to the concept that ketamine's analgesic and anaesthetic effects are mediated by separate mechanisms. The stereospecific binding of (+)ketamine to opiate receptors in vitro, more rapid emergence from anaesthesia, and the lower incidence of emergence sequelae, make (+)ketamine a promising drug for future research. Clinical applications of ketamine that have emerged recently, and are likely to increase in the future, are the use of oral, rectal, and intranasal preparations for the purposes of analgesia, sedation, and anaesthetic induction. Ketamine is now considered a reasonable option for anaesthetic induction in the hypotensive preterm neonate. The initial experience with epidural and intrathecal ketamine administration has not been very promising but the data are only preliminary in this area. The use of ketamine in military and catastrophic settings is likely to become more common. The clinical availability of midazolam will complement ketamine anaesthesia in several ways. This rapidly metabolized benzodiazepine reduces ketamine's cardiovascular stimulation and emergence phenomena, and does not have active metabolites. It is dispensed in an aqueous medium, which is usually non-irritating on intravenous injection, unlike diazepam. The combination of ketamine and midazolam is expected to achieve high patient acceptance, which never occurred with ketamine as a sole agent. Finally, it is necessary to point out the potential for abuse of ketamine. While ketamine is not a controlled substance (in the United States), the prudent physician should take appropriate precautions against the unauthorized use of this drug.
Fifty patients undergoing endoscopy (laryngoscopy, bronchoscopy, mediastinoscopy) were anaesthetised in a double-blind prospective trial using total intravenous anaesthesia. Half of the patients were anaesthetised with an infusion of a solution of 250 mg ketamine and 12.5 mg midazolam. The other patients received an infusion of a solution of 250 mg ketamine and 20 mg diazepam. In addition, both groups were given increments of 50-100 micrograms of fentanyl. The immediate awakening time (t1) was not significantly different between groups, but the patients who had received midazolam-ketamine, had a significantly shorter time to more complete recovery (t2), a significantly lower frequency of emergence reactions and were more satisfied with the anaesthetic than the patients who had received diazepam-ketamine. There was no difference between groups with respect to intraoperative heart rate and blood pressure. No awareness during anaesthesia was reported.
Plasma ketamine concentrations after diazepam and placebo pretreatment were examined in a double-blind, randomized, cross-over study. Eight healthy male subjects received either diazepam or a 0.9% NaCl placebo before ketamine and received the alternate combination 5 to 24 days later. Ten minutes before ketamine dosing, diazepam, 0.3 mg/kg, or placebo in equal volume was injected intravenously at a rate not exceeding 5 mg/min. Ketamine, 2.2 mg/kg iv, was injected over 1 min. For the clinically relevant period for anesthesia (1 to 30 min), diazepam-ketamine treatment resulted in higher plasma levels at most time points, but diazepam pretreatment did not alter plasma levels of metabolite KI and pseudometabolite KII nor the 24-hr urinary excretion of ketamine, KI, and KII. Ketamine kinetics followed a three-term exponential decline under both treatment conditions. After placebo-ketamine dosing, plasma t½s were as follows: distribution (t½) = 24.1 sec, redistribution (t½) = 4.68 min, and elimination (t½) = 2.17 hr. After diazepam-ketamine dosing, t½s were: t½ = 25.0 sec, t½ = 6.37 min, and t½ = 2.32 hr.
Six healthy, consenting volunteer males received ketamine iv in five logarithmically scaled doses totaling 3 mg/kg on three occasions each. The sessions differed only in the initial injection of an unknown drug: placebo, morphine sulfate 0.2 mg/kg, or morphine sulfate 0.4 mg/kg. Initial and terminal steady-state ventilatory responses to CO2 (VERCO2) and isohypercapnic ventilation (end-tidal CO2 49.8 +/- 2.4 mmHg) during drug administration assessed CO2-mediated ventilatory drive. Oxygen concentration of 40% ablated hypoxic drive contribution. Morphine caused a decrease of isohypercapnic ventilation (VE) of 8.2 +/- 1.2 l/min after 0.2 mg/kg. Doubling the dose to 0.4 mg/kg gave a further depression of 6.6 +/- 1.8 l/min. No subject lost consciousness after morphine. Over a dose range of 0.39 to 3.0 mg/kg ketamine caused log-linear dose-related depression of 1.6 +/- 0.3 l/min for each doubling of dose, although the first significant depression of 4.9 +/- 1.1 l/min did not occur until the third dose (1.1 mg/kg) in the absence of morphine. All subjects were unconscious after 1.8 mg/kg ketamine. Slopes of the VERCO2 did not differ from control, regardless of the pretreatment, placebo, or morphine in the two doses. Ketamine alone, 3.0 mg/kg, caused a displacement of VERCO2 of +2.0 +/- 1.2 mmHg in CO2, while combination of ketamine and morphine in either dose caused a +10 mmHg displacement of VERCO2. Thus, ketamine appears qualitatively similar but less potent than premedicant doses of morphine in depressing respiration despite near equipotency in producing loss of consciousness.
In nine patients with cortical, limbic and thalamic electrode implants, correlative electrical activity and gross behavior were observed following administration of ketamine, 70 per cent N2O, and thiopental. Ketamine was administered in four dosages: 0.5, 1, 2, and 4 mg/kg. One patient who received 0.5 mg/kg iv manifested depth-clectrode seizure activity without loss of consciousness. Two patients, receiving 1 mg/kg iv, developed increased frequency in their depth-clectrode EEC's with transient unconsciousness. All six patients receiving 2 or 4 mg/kg iv developed electrical seizure activity in the limbic and thalamic areas, with uncorrected behavioral manifestations ranging from apparent "unconsciousness" and immobility to actual tonic and clonic motor activity. The surface EEG did not manifest the intense electrical activity in the limbic region at all times. In contrast, administration of 70 per cent N:O and 400 mg thiopental did not induce electrical seizure phenomena. It is suggested that ketamine be used cautiously in patients with seizure disorders.
In 150 children, atropine and diazepam 0.2 mg kg-1 were given i.m. 1 h before the rectal administration of ketamine 8-10 mg kg-1 (to a maximum of 150 mg). A 1% solution was used for children weighing less than 15 kg and a 5% solution for those weighing more. When the required level of sedation was obtained, anaesthesia was maintained and controlled by the use of enflurane in nitrous oxide and oxygen, with spontaneous ventilation via a face mask. Induction was judged excellent in 139, good in seven and fair in four instances. Amnesia for induction was complete in 75% of the patients.
One hundred and eleven patients undergoing ketamine anaesthesia for therapeutic abortion were studied in a double-blind trial of the reversal of ketamine by physostigmine administered postoperatively. The results demonstrate that physostigmine does not shorten recovery time or reduce the occurrence of ketamine emergence phenomena such as hallucinations, restlessness and dreams. In fact, the recovery course was prolonged in patients given physostigmine immediately upon termination of anaesthesia as compared with controls. By contrast, when physostigmine was given 30 minutes after the last dose of ketamine, the recovery was not prolonged as compared with that of the placebo-treated controls. These findings suggest some synergism between the effects of ketamine and physostigmine and should discourage the use of physostigmine as a ketamine antidote.
In 16 adult patients, IV ketamine, 2.2 mg/kg body weight, did not produce dramatic effects on left heart function or systemic circulation. Minute O2 consumption and O2 delivery were stable. An appreciable elevation in pulmonary vascular resistance occurred which secondarily increased right heart work. Total intrapulmonary shunt initially increased; however, the effect was short lived and did not cause clinical alterations in PaO2. The authors conclude that physiologic alterations associated with ketamine are more pronounced on the pulmonary than on the systemic vascular bed, and to the right rather than to the left side of the heart.
Thirty consecutive patients with angiographically demonstrated coronary artery disease randomly received anesthesia either with morphine, diazepam, nitrous oxide in oxygen, and pancuronium (group 1—16 patients), or with ketamine, nitrous oxide in oxygen, and pancuronium (group 2—14 patients). The incidence of intraoperative complications was the same in both groups: hypertension occurred in nine patients of group 1 and six in group 2; ventricular arrhythmias, two in group 1 and one in group 2; death, one in each group. Incidence of postoperative complications was also similar. Although the incidence of hemodynamic changes was similar, the degree of maximal change in systolic blood pressure differed between groups. The mean maximal increase in systolic BP was significantly greater in group 2 (33% of control) than group 1 (16%). The maximal decrease in systolic BP was significantly greater in group 1 (18% of control) than group 2, and the duration of hypotension was significantly greater in group 1 (9.1 minutes) than group 2 (no hypotension). Peak changes in heart rate/systolic blood pressure product (RPP) increased significantly from control in both groups (group 1, 34% and group 2, 71%). Although the percent change in group 2 is twice that in group 1 at peak hypertension, the RPP values were not significantly different. The incidence and degree of hypertension in both groups were unrelated to preoperative ventricular function. We conclude that the morphine anesthetic technic was superior to the ketamine technic in this study, but that neither anesthetic regimen adequately controls the autonomic nervous system in patients with ischemic heart disease.
In 14 patients undergoing open-heart operations the haemodynamic effects of diazepam 0.4 mgkg(-1) followed by ketamine 2 mg kg(-1) were studied. In eight patients undergoing coronary bypass surgery, the mean arterial pressure decreased significantly after diazepam from 90.3 +/-7.4 (SEM) to 78.0 +/-5.0 mm Hg (P less than 0.05). However, no changes occurred in six patients undergoing valve replacement. The subsequent administration of ketamine produced no significant changes in mean arterial pressure. No signfiicant change in heart rate occurred in any patient at any time during the period of study. No patient reported unpleasant emergence reactions after operation.
Premedication with diazepam, hydroxyzine or secobarbital significantly increased ketamine-induced sleep time (137 +/- 3.5 min, 135 +/- 9.2 min, 128 +/- 4.7 min) over that of unpremedicated controls (98.5 +/- 4.4 min) in man. The corresponding mean plasma half-lives (t1/2) of ketamine were longer in patients premedicated with diazepam or seconbarbital (57.8 +/- 4.9 min, 46 +/- 3.2 min) than in controls (36 +/- 1.8 min). Ketamine t1/2 in the perfusate of isolated, perfused rat livers was prolonged 30 to 50 per cent by addition of diazepam, secobarbital, or hydroxyzine. The data suggest that these commonly used premedicants decrease the rate of ketamine metabolism.
Rectally administered midazolam (0.30 mg/kg) and ketamine (5 mg/kg) were compared for preanesthetic medication in children undergoing dental extractions. Sixty patients between the ages 2 and 9 years were randomly allocated to three groups in this double-blind study. In one group of patients who received ketamine rectally, intravenous midazolam (0.05 mg/kg) also was administered immediately after induction of anesthesia. The results from this trial show that 30 minutes after rectal administration of the two drugs, good anxiolysis, sedation, and cooperation were obtained in most patients. Although midazolam appeared to be marginally more efficacious than ketamine in the majority of assessments made and seemed to have less adverse effects, no statistically significant differences could be shown. Ketamine showed a slight decrease and midazolam a slight increase in average blood pressures after premedication. These blood pressure differences were, however, considered to be of little clinical importance.
In a single-blind controlled study, forty children with congenital heart disease were premedicated with oral trimeprazine 3 mg/kg and either intramuscular morphine 0.1 mg/kg or oral ketamine 10 mg/kg. Cardiovascular and respiratory effects of premedication and degree of sedation induced were similar in the two groups of patients. Oral ketamine is a safe and effective premedicant in this group of patients.
We describe a prospective study of 18 pediatric ophthalmic patients given low-dose intramuscular ketamine hydrochloride as the sole or adjunct anesthetic agent. Our results indicated that there was a low incidence of side effects with successful operative outcomes.
This study compares the quality of anesthesia achieved with low-dose ketamine with that of methohexital sodium. In a double-blind study of 40 healthy adult patients undergoing a variety of minor oral surgical procedures, the anesthetic techniques were assessed with respect to the following parameters: patients' subjective evaluation of the anesthesia, the level of response to injection of local anesthetic, psychomotor ability after surgery, recovery times, and the frequency of adverse effects. From these observations, it was deduced that when low-dose ketamine was used with diazepam, meperidine, and nitrous oxide, it proved to be a safe and effective supplement for minimizing pain, discomfort, and anxiety before injection of local anesthetic. Patients' appreciation of the level of anesthetic achieved, psychomotor ability, adverse reactions, and recovery time was not significantly different from the methohexital sodium group.
Fifteen healthy children 2-10 years old and scheduled for elective surgery, received midazolam 0.35 mg/kg body weight and atropine 0.025 mg/kg as rectal premedication about 35 min before the induction of anesthesia. The induction itself was carried out in a separate and quiet room next to the operating theatre by rectal administration of ketamine 10 mg/kg and midazolam 0.2 mg/kg. With the children breathing spontaneously, anesthesia was maintained by repetitive i.v. bolus injections of ketamine. The sedative and anticholinergic effects of the premedication were satisfactory. Induction of anesthesia was smooth. Consciousness was lost after 9-15 (mean 13) min. No significant adverse effects on hemodynamics or respiration were noted. Recovery from anesthesia was uneventful. No cases of rectal irritation or unpleasant dreams were reported. Post-operative analgesia was good. In conclusion, rectal administration of midazolam and atropine for premedication, followed by ketamine and midazolam for the induction of anesthesia, proved to be a pleasant, safe, and reliable method in pediatric anesthesia.
Dissociative-sedation, a sedation technique found to be particularly applicable in the pediatric dental patient will be presented in this article. No attempt should be made by the inexperienced dentist to produce the state described. Rather, consultation with and referral to an appropriately trained physician or dental anesthesiologist is in order.
We studied ketamine intravenous regional anesthesia of the upper extremity in volunteers using concentrations of 0.5%, 0.3%, and 0.2%. Ketamine 0.5 and 0.3% produced adequate intravenous regional anesthesia. Anesthesia was inadequate when a 0.2% concentration was used. However, although the 0.3% concentration provides complete sympathetic, sensory, and motor blockade when injected into the isolated extremity, unpleasant psychotomimetic effects after the release of the tourniquet limit the usefulness of this use of ketamine. Ketamine cannot be recommended for intravenous regional anesthesia unless these unpleasant side effects are abolished or controlled by means of pharmacologic adjuvants.
Ketamine has many neuromuscular effects in vitro. Its neuromuscular effects in vivo have been controversial and inconsistent. To systematically examine its neuromuscular effects over a wide dose range and its interaction with all popular nondepolarizing neuromuscular relaxants, the effects of ketamine 2, 5, and 10 mg/kg IV were studied on a continuous but incomplete (50%) neuromuscular block preestablished by an IV infusion of d-tubocurarine, atracurium, vecuronium, and pancuronium. Indirectly stimulated adductor pollicis muscle response of monkeys anesthetized with 0.5-1.0% halothane in oxygen were quantified. Ketamine in the absence of a neuromuscular relaxant had no effect on the thumb twitch. In a dose-dependent manner, ketamine significantly enhanced the 50% depression of the thumb twitch preestablished by a constant IV infusion of each of the four muscle relaxants studied. Ketamine 2 mg/kg potentiated the neuromuscular relaxants in the following order of magnitude: vecuronium greater than atracurium greater than d-tubocurarine greater than pancuronium. However, with a 10 mg/kg dose of ketamine, pancuronium became as potentiated as was vecuronium, i.e., pancuronium = vecuronium greater than atracurium greater than d-tubocurarine. It is concluded that in the primate, ketamine potentiates all nondepolarizing muscle relaxants in a dose-dependent manner.
The bronchodilator effects of ketamine were examined in human bronchial preparations contracted maximally with histamine,
acetylcholine, barium chloride or potassium chloride. Antagonism between ketamine and either histamine or acetylcholine was
examined also. Ketamine caused bronchial relaxation irrespective of the constricting agent, and exerted a partial and non-competitive
antagonism to histamine and acetylcholine. Propranolol and indomethacin did not inhibit the effect of ketamine, excluding
the involvement of β activation and of prostaglandins.
We have studied the pharmacokinetics of ketamine administered rectally in a dose of 10 mg kg−1 to five children aged 6–9 yr and mean weight 28.80 (SD 6.55) kg. An acceptable level of anaesthesia was not obtained in any
patient. Despite this, the degree of analgesia obtained was good and no child required further administration of analgesics
during the postoperative period. Tolerance to the suppositories was excellent. The absorption of ketamine was found to be
relatively fast, with a median peak concentration of 160 ng ml−1 (range 96–250 ng ml−1) at 0.75 h (range 0.50–1.00 h) after administration. The plasma concentrations of norketamine were greater than those of
the parent drug, with a maximum of 510 ng ml−1 (range 450–810 ng ml−1) at 0.81 h (range 0.50–1.00 h) after administration. The medians of the half-lives of ketamine and norketamine were 3.15
h and 2.56 h, respectively (range 1.57–4.95 h and 1.47–5.30 h, respectively).
Renewed interest in i.v. anesthetic techniques has resulted from the availability of more rapid and shorter-acting i.v. drugs. With recent advances in the area of infusion pump technology, it has become easier to administer i.v. anesthetics and analgesics by continuous infusion techniques. The newer sedative-hypnotic (midazolam, propofol) and analgesic (sufentanil, alfentanil) drugs are better suited pharmacologically to continuous administration techniques than the traditional i.v. agents because they can be more accurately titrated to meet the unique and changing anesthetic needs of the individual patient. With the newer sedative and analgesic drugs, it is now possible to administer i.v. anesthetics in a titrated manner analogous to that which is possible when volatile anesthetics are used. In this way, the drug infusion rate is varied depending on the patient's responses to noxious surgical stimuli. In titrating i.v. drug infusions, consideration must also be given to the age of the patient, pre-existing disease states, potential drug interactions, and proximity to the end of the operative procedure. The availability of rapid and short-acting i.v. drugs like alfentanil and propofol, as well as intermediate-acting muscle relaxants makes it possible to employ total intravenous anesthetic techniques during general surgery. Many non-sedative and non-analgesic i.v. drugs are being investigated in anesthesia for use by continuous infusion techniques, e.g., muscle relaxant, and local anesthetics. Several recent studies have demonstrated the efficacy of continuous infusions of local anesthetics for obstetrical analgesia. The use of continuous local anesthetic infusions makes it possible to achieve improved analgesia (i.e., a more constant degree of analgesia) with lower doses. Improved delivery systems for administering i.v. drugs will make it easier to use continuous infusion techniques in the future. With continued progress in the development of infusion devices and i.v. drugs designed for continuous administration, the use of intravenous anesthetic techniques will become more widespread. In the near future, infusion pumps will likely become standard equipment on all anesthesia machines and anesthesiologists should find these techniques easier to use in their clinical practices.
Cardiovascular, respiratory, CNS, and postoperative effects of using low-dose ketamine and midazolam combined with local anesthesia during 40 outpatient cosmetic procedures are reviewed. This method of anesthesia is safe, effective, and well-tolerated by patients.
The use of ketamine in individuals susceptible to malignant hyperthermia (MH) is controversial. We describe our experience with ketamine used for induction and/or maintenance of anesthesia in our herd of swine inbred for susceptibility to MH. A total of 76 MH-susceptible swine were given a total of 112 general anesthetics using ketamine as the induction drug. In 34 of these anesthetics, anesthesia was also maintained with ketamine. Signs of MH did not develop in response to ketamine in any of the pigs.
Physical compatibilities of infusion solutions containing ketamine and diazepam or midazolam in different concentrations were studied by visual examination and by light-scattering measurements. The isotonic infusion solutions used were fructose 5%, glucose 5%, and NaCl 0.9%. The concentration of additive were between 500 and 600 mg ketamine, 60 and 100 mg diazepam and 30 and 60 mg midazolam (Dormicum) per liter intravenous solution. During a period of 24 h the solutions remained colorless without demixing, precipitation, or changes in pH. The light-scattering measurements were performed immediately after preparation of the solution and repeated after 1, 4, 8, and 24 h using monochromatic light at a wavelength lambda 0 = 546 nm and temperatures T = 20 degrees and 37 degrees C. The light-scattering measurements showed that all intravenous solutions were physically true, homogeneous solutions with no change over a period of 24 h within experimental error, i.e. the solution behavior remained constant. A small amount of the dissolved particles (less than 0.5%) had diameters of 1-4 microns whereas those of all other particles were smaller than 0.02 microns. The particles with 1 to 4 microns diameter consisted of aggregates of the dissolved substances called microgels. Removal of both microgels and inorganic and organic dust is possible with filters of pore size 0.5 microns or by centrifugation at 10,000 rpm. In clinical practice filtering is much more feasible.
Analgesia induced by ketamine appears to be partially mediated by opiate mechanisms. Not only is its action attenuated by the narcotic antagonist naloxone, but the drug has a weak affinity for, and interacts stereoselectively at, opiate receptors. It also produces a classical narcotic action on the guinea-pig ileum. The present study showed that analgesic doses of the drug in rats yielded concentrations sufficient to interact effectively at opiate binding sites in vivo. A dose-dependent (80-120 mg/kg i.p.) inhibition of the binding of [3H]naloxone was observed in both brain and spinal cord. All regions of the brain (except the cerebellum) were affected, but the reduction was significant in the cortex, hippocampus, thalamus and striatum. Thus, a component of ketamine-induced analgesia could be related to a functional interaction with opiate receptors. Additionally, ketamine may be similar to morphine in its preference for the mu, rather than the delta sub-type of opiate receptors, and thus may promote mu-mediated pharmacological effects. For example, in vitro studies of radioligand binding showed that ketamine and morphine were four times more effective in inhibiting the binding of [3H]dihydromorphine than that of [3H] [D-Ala2, D-Leu5] enkephalin. On the other hand, ketamine also effectively interacted at a component of the sigma opiate/phencyclidine binding sites that appears to be relatively insensitive to morphine. This component may be involved in dysphoria induced by ketamine.
The behavioral effects of MK-801 [(+)-5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-imin e], a proposed noncompetitive N-methyl-D-aspartate (NMDA) antagonist, were compared to those of phencyclidine (PCP). In pigeons, MK-801 produced PCP-like catalepsy (i.e., loss of righting without eye closure and without muscle relaxation) and PCP-like discriminative stimulus effects. In rats, MK-801 produced PCP-like behavior (i.e., locomotion, sniffing, swaying and falling). In rhesus monkeys, like PCP, MK-801 produced 1) ketamine-like discriminative stimulus effects, 2) positive reinforcing effects and 3) ketamine-like anesthetic effects (i.e., anesthesia without eye closure and without respiratory depression, but with profuse salivation and with some muscle relaxation). Thus, MK-801 produced PCP-like behavioral effects in each species and with each procedure. MK-801 was 2 to 10 times more potent than PCP, depending on the effect measured and the species tested. Because MK-801 has been shown to have NMDA-antagonist properties, the findings of this study offer further support for the hypothesis that certain behavioral effects of PCP-like drugs may result from a reduction of neurotransmission at excitatory synapses utilizing NMDA-preferring receptors. The behavioral similarities between MK-801 and PCP make it relevant to evaluate PCP-like activity in clinical trials of MK-801.
The authors sought to determine whether intramuscular ketamine (2 mg/kg) would facilitate inhaled induction of anesthesia in those children who are uncooperative. Thirty-five children were anesthetized with halothane and nitrous oxide for insertion of tympanotomy tubes. Twenty of those children were deemed by the anesthesiologist to be uncooperative and received 2 mg/kg of ketamine im prior to induction of anesthesia. The onset time (time from ketamine administration until induction of inhaled anesthesia could be started) was 2.7 +/- 0.3 min. The quality of the subsequent acceptance of inhaled induction with halothane was excellent in 61% of the patients and adequate in the remaining 39%. The recovery and discharge times were compared with those observed in 15 matched children who accepted induction of anesthesia via a mask without the use of ketamine. Recovery time was not prolonged, but home discharge was delayed by an average of 13 min in the ketamine group (P less than 0.04). Low-dose im ketamine was found to be an acceptable pre-induction drug in young children who are uncooperative for an inhaled induction of anesthesia.
The binding specificity of (+)-[3H]N-allylnormetazocine, the dextrorotatory isomer of the prototypical sigma opiate SKF10,047, was determined in rat and mouse brain and the neuroanatomical distribution of its binding sites elucidated by quantitative autoradiography in sections of rat brain. Computer-assisted Scatchard analysis revealed an apparent two-site fit of the binding data in both species and in all rat brain regions examined. In whole rat brain, the Kd values were 3.6 and 153 nM and the maximum binding values were 40 fmol and 1.6 pmol/mg of protein for the apparent high- and low-affinity binding sites, respectively. (+)-SKF10,047, haloperidol and pentazocine were among the most potent inhibitors of 7 nM (+)-[3H]SKF10,047 binding to the higher affinity sites; rank orders of ligand potencies at these sites differ sharply from those that have been reported for the [3H]phencyclidine (PCP) site, or for eliciting PCP-like or SKF10,047-like behaviors. By contrast, rank orders of potency of sigma opiods, PCP derivatives and dioxolanes for displacement of 100 nM (+)-[3H]SKF10,047 from the more numerous lower affinity sites in the presence of 100 nM haloperidol agreed closely with their potencies in the [3H]PCP binding assay as well as their potencies in exerting PCP- or SKF10,047-like behavioral effects. In order to compare directly the anatomical localizations of PCP and (+)-SKF10,047 binding sites, quantitative light microscopy autoradiography utilizing tritium-labeled PCP and (+)-SKF10,047 was carried out in rat brain sections. (+)-[3H]SKF10,047 binding was observed to follow the regional pattern of [3H]PCP binding but also to bind in other regions not associated with PCP receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
This study was done to investigate the effectiveness and safety of ketamine analgesia after halothane anesthesia for surgery in children. After completion of a surgical procedure, ten children had ketamine (1 mg/kg) injected intravenously during maintenance of anesthesia with 1% halothane in a 60:40 nitrous oxide-oxygen mixture. Cardiovascular parameters measured with noninvasive oscillometry and transthoracic impedance plethysmography remained unchanged after administration of ketamine. Excellent analgesia and a calm anesthetic recovery were produced, without detectable cardiovascular depression. When ketamine and halothane are administered in combination, careful restriction of dosages of these agents is recommended. Interaction of higher doses of ketamine and halothane has been reported to produce hypotension and bradycardia, which can be avoided with use of subdissociative, analgesic doses of ketamine during light halothane maintenance before emergence. After halothane anesthesia in healthy children, ketamine may be considered a suitable alternative to narcotics for postoperative analgesia.
The relative efficacy and safety of drugs and combinations used clinically in dentistry as premedicants to alleviate patient apprehension are largely unsubstantiated. To evaluate the efficacy and safety of agents used for parenteral sedation through controlled clinical trials, it is first necessary to identify which drugs, doses, and routes of administration are actually used in practice. A survey instrument was developed to characterize the drugs used clinically for anesthesia and sedation by dentists with advanced training in pain control. A random sample of 500 dentists who frequently use anesthesia and sedation in practice was selected from the Fellows of the American Dental Society of Anesthesiology. The first mailing was followed by a second mailing to nonrespondents after 30 days. The respondents report a variety of parenteral sedation techniques in combination with local anesthesia (the response categories are not mutually exclusive): nitrous oxide (64%), intravenous conscious sedation (59%), intravenous "deep" sedation (47%), and outpatient general anesthesia (27%). Drugs most commonly reported for intravenous sedation include diazepam, methohexital, midazolam, and combinations of these drugs with narcotics. A total of 82 distinct drugs and combinations was reported for intravenous sedation and anesthesia. Oral premedication and intramuscular sedation are rarely used by this group. Most general anesthesia reported is done on an outpatient basis in private practice. These results indicate that a wide variety of drugs is employed for parenteral sedation in dental practice, but the most common practice among dentists with advanced training in anesthesia is local anesthesia supplemented with intravenous sedation consisting of a benzodiazepine and an opioid or a barbiturate.
Previous studies have shown that ketamine interacts with opiate receptors, and it has been suggested that ketamine-induced analgesia is mediated through opiate receptors. If so, ketamine should produce less analgesia in morphine tolerant animals, just as morphine does. To test this hypothesis, the analgesic effects of ketamine were tested in mice implanted with placebo pellets and in mice made tolerant to morphine through implantation of morphine pellets, using the abdominal constriction test. The test consisted of ip injection of 1% acetic acid, which caused stretching of hind limbs and constriction of abdominal muscles, also called writing. The number of writhes was counted for each mouse 10-15 min following acetic acid injection. Morphine pellet implanted mice treated with saline writhed 12.2 +/- 0.8 times (mean +/- SEM), not significantly different from 9.8 +/- 0.9 times seen in placebo pellet implanted mice. Treatment of the animals with ketamine at three doses of 20, 25, and 30 mg/kg, subcutaneously (sc), reduced the number of writhes in the placebo pellet implanted group to 5.8 +/- 0.8, 4.2 +/- 0.7, and 1.3 +/- 0.3, respectively. In the morphine pellet-implanted group, with the same doses of ketamine, the numbers of writhes were 10 +/- 0.9, 9.3 +/- 1.1, and 5.2 +/- 0.9, respectively. Morphine-tolerant animals writhed significantly more at each dose of ketamine, indicating that they were cross tolerant to the analgesic effects of ketamine.
The effect of ketamine administration on the ventricular arrhythmogenic dose of epinephrine ( vade ) was studied in 4 halothane-anesthetized cats. Each cat was anesthetized 4 times, 1 week apart, with halothane (end-tidal concentration, 1.5%) and with halothane (end-tidal concentration, 1.5%) combined with ketamine infusion (50, 100, and 200 μg/kg of body weight/min). Epinephrine was infused in progressively increasing doses. The vade (μg/kg) was calculated as the product of infusion rate of epinephrine and time of infusion necessary to induce 4 or more ventricular premature depolarizations within 15 s. The mean (± sd ) vade during halothane anesthesia was 1.1 (± 0.30) μg/kg. Ketamine infusion significantly ( P < 0.01) lowered the vade independently of dose. The dose of epinephrine (μg/kg) that induced an ecg change in P-wave configuration was calculated similarly. Less epinephrine was necessary to induce a change in P-wave configuration than was necessary to induce 4 or more ventricular premature depolarizations within 15 s.
Blood samples were collected after 4 hours of ketamine infusion and again immediately after determination of the vade for analysis of plasma ketamine and norketamine concentrations by use of gas chromatography. Plasma ketamine and norketamine concentrations after a 4-hour infusion and immediately after determination of the vade were similar for any given ketamine infusion rate, indicating that steady-state plasma concentrations had been reached for each infusion rate.
Blood pressure and heart rate were measured immediately before (base line) and immediately after infusion of the vade . Ketamine infusion significantly ( P < 0.05) lowered base-line blood pressure, but not heart rate. Blood pressure and heart rate associated with the vade increased from base-line values, regardless of the ketamine infusion rate. These results suggested that ketamine administration lowers the vade in halothane-anesthetized cats.
The effects of atelectasis on pulmonary gas exchange were studied in eight supine, clinically lung-healthy patients. Atelectasis was studied by computerized tomography (CT), and gas exchange by blood gas analysis. The distribution of ventilation/perfusion ratios was assessed by a multiple inert gas elimination technique. No patient had any signs of atelectasis in the awake state, and gas exchange was normal. During ketamine anaesthesia and spontaneous breathing, lung ventilation and perfusion were well matched in most subjects. In one patient there was perfusion of poorly ventilated regions amounting to 14% of cardiac output, and in another there was a shunt of 4% of cardiac output; this patient was the only one who developed atelectasis in dependent lung regions. After muscular relaxation and commencement of mechanical ventilation, all patients but one developed both shunt (2-6% of cardiac output) and atelectasis. The shunt correlated to the size of atelectasis. It is concluded that the occurrence of shunt during anaesthesia is related to the development of atelectasis in dependent lung region, which is consistent with the hypothesis that it is changes in chest-wall mechanics that cause atelectasis.
A patient with acute lymphatic leukaemia developed a bilateral fulminating Pseudomonas aeruginosa pneumonia and required controlled ventilation of the lungs. Marked agitation, hypotension and bronchospasm unresponsive to conventional bronchodilators presented a therapeutic challenge. A continuous intravenous infusion of midazolam failed to provide adequate sedation. A continuous intravenous infusion of ketamine resulted in better sedation, an increase in arterial pressure and a diminution of bronchospasm. The clinical improvement was maintained for the 5 days during which ketamine was infused. Plasma concentrations of ketamine and its metabolites are reported.
We treated two pediatric patients suffering respiratory failure associated with status asthmaticus. Neither patient responded to maximal bronchodilatory therapy and mechanical ventilation; however, continuous infusion of ketamine (1.0 to 2.5 mg/kg X h) immediately improved airway obstruction. Ketamine appears to increase catecholamine levels and directly relax bronchial smooth muscle. Except for increased secretions during the infusion, our patients showed no immediate or long-term sequelae from ketamine therapy. However, ketamine should only be used for asthmatics whose respiratory failure does not respond to conventional management and mechanical ventilation.
Both ketamine and tracheal intubation are associated with increased heart rate (HR) and systolic blood pressure (SBP). Beta blockers prevent or attenuate this increase. Esmolol (E) is a new, intravenous, rapidly metabolized beta blocker. An open-label study was performed in 41 ASA Class II and III patients divided into groups 1-4: control, 100, 200, and 300 micrograms X kg-1 X min-1 (n = 10, 10, 11, and 10, respectively). E was infused over 10 min, the first one-fourth of which was a loading dose of 500 micrograms X kg-1 X min-1; at 4 min, ketamine was followed by succinylcholine, intubation, and enflurane-N2O-O2. HR, SBP, blood E, and plasma catecholamine levels were obtained during the 40 min of study. The control group had a baseline HR of 83 +/- 5 beats/min while esmolol groups 2-4 had an HR of 73 +/- 3, 72 +/- 3, and 68 +/- 4 beats/min, respectively (P less than 0.05). After ketamine, the control group HR increased to 93 +/- 6 beats/min and groups 2-4 remained at the baseline level, 73 +/- 3, 73 +/- 3 and 67 +/- 4 beats/min, respectively (P less than 0.05). Postintubation, the control increased further to 113 +/- 5 beats/min while groups 2-4 were significantly less, 91 +/- 5, 84 +/- 3, and 78 +/- 4 beats/min, respectively. The mean SBP in most E groups was less than the control within groups, but only in group 4 between groups was the SBP less at postintubation (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
In a double-blind study, the effects of atropine and glycopyrrolate (dosage ratio 2:1) following i.m. and i.v. administration were compared with respect to salivation, heart rate, and blood pressure before, during and after i.v. infusion anaesthesia with ketamine and diazepam for alloplastic hip or knee surgery in 30 patients above the age of 50 years. Given with the premedicant, the two drugs were equally effective in reducing salivation. A slight increase in heart rate was seen after atropine only (P less than 0.005). Increases in heart rate and blood pressure during induction of anaesthesia were similar in the two groups. A second dose of the test drug was given with neostigmine for reversal of neuromuscular blockade. Again, there were no statistically significant differences with respect to salivation, blood pressure, heart rate, nausea and/or vomiting, unpleasant dreams and arousal time.
The authors compared the respiratory effects of an intravenous infusion of ketamine (1 mg X kg-1) with droperidol (0.1 mg X kg-1), or placebo on three different occasions in a double-blind, randomized fashion in eight healthy volunteers. Breathing pattern, thoraco-abdominal motion, end-expiratory positions of the rib cage and abdomen, arterial hemoglobin oxygen saturation (SaO2), and end-tidal carbon dioxide concentration (FECO2) were continuously measured with noninvasive techniques. During the 1-h monitoring period following drug injection, droperidol produced occasionally significant but clinically unimportant differences in respiratory variables when compared with placebo. In contrast, ketamine induced a significant (P less than 0.001) and persistent increase in minute ventilation (+75%) from 5 to 20 min after start of infusion by increasing both the driving (i.e., tidal volume/inspiratory time [VT/Ti]) and the timing (i.e., inspiratory time/total respiratory cycle time [Ti/Ttot]) components of ventilation (Milic-Emili J, Grunstein MM: Chest 70 (Suppl): 131-133, 1976). This was obtained without any significant change in end-expiratory positions or change in relative rib cage contribution to tidal volume. Despite multiple apneic episodes observed with ketamine, the subjects maintained a stable SaO2 and FECO2, indicating no resting respiratory depression. This study, performed with a noninvasive respiratory monitoring technique, confirms that droperidol infused over 5 min at a clinically used dosage does not cause respiratory depression in healthy subjects, whereas ketamine produces an important ventilatory stimulation.
The effects of anesthetic doses of ketamine (iv bolus of 3 mg X kg-1 followed by a continuous infusion of 20 micrograms X kg-1 X min-1) on functional residual capacity (FRC) measured by the helium dilution method and on the breathing pattern recorded by a noninvasive method (NIM) based on chest wall circumference changes were studied in 14 ASA P.S. I patients. Ketamine anesthesia was associated with: 1) the maintenance of FRC, minute ventilation, and tidal volume; 2) an increase in rib cage contribution to tidal breathing; and 3) an alteration of volume-motion relationships of the chest wall compartments. It is concluded that: 1) in contrast to volatile anesthetic agents, ketamine anesthesia has a sparing effect on intercostal muscle activity, which may explain the maintenance of FRC; and 2) changes in chest wall geometry and compliance induced by anesthetic agents must be taken into account for NIM to be valid.
