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ABSTRACT: When anesthetizing children with congenital heart disease for diagnostic cardiac catheterization, anesthesiologists and cardiologists seek to use anesthetic regimens that yield minimal hemodynamic changes and allow for spontaneous ventilations. Recently, dexmedetomidine has been used as an anesthesia adjunct because of its sedative and analgesic properties and minimal ventilatory depressive effects. We tested the hypothesis that the combination of sevoflurane and dexmedetomidine is non-inferior to sevoflurane alone as it refers to hemodynamic measurements during diagnostic cardiac catheterization in children with a transplanted heart, one ventricle (Fontan procedure), or normal cardiac physiology. Patients were anesthetized with inhalation of sevoflurane in nitrous oxide/oxygen and, after baseline hemodynamic measurements, successive boluses of dexmedetomidine followed by continuous infusion were administered. In this study, non-inferiority was shown when differences at steady-state (dexmedetomidine + sevoflurane) compared to baseline (sevoflurane alone) and its associated 95% confidence interval fell completely within the range of plus or minus 20%. Forty-one (26 normal physiology, 9 cardiac transplantation, and 6 Fontan) patients were enrolled. Non-inferiority of sevoflurane + dexmedetomidine compared with sevoflurane alone was shown for heart rate, but not for arterial blood pressure in patients with normal and cardiac transplant physiology. In patients with normal cardiac physiology, non-inferiority was demonstrated for bispectral index. Therefore, while the lack of depressive respiratory effects and non-inferiority for heart rate are desirable, the lack of non-inferiority of dexmedetomidine + sevoflurane combination for arterial blood pressure do not justify the routine use of this combination compared with sevoflurane alone for children with congenital heart disease undergoing cardiac catheterization.
Pediatric Cardiology 11/2012; · 1.30 Impact Factor
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ABSTRACT: Parental presence during induction of anesthesia is a common practice to allay perioperative anxiety in the pediatric population. We present the first documented case in the anesthesia literature of parental interruption of induction of anesthesia. The report is to inform practitioners of the need for perioperative screening, education, and contingency planning to prepare for the possibility of familial disruption during pediatric inductions, cesarean deliveries, and other practice settings that may have lay people present.
Anesthesia and analgesia 08/2012; · 3.08 Impact Factor
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ABSTRACT: Niemann-Pick disease type C, an autosomal recessive lysosomal storage disorder, can present with severe visceral and neurologic involvement and is associated with a significant decrease in life expectancy. As little is known about anesthetic considerations of this disease, we examined the perianesthetic course of patients with Niemann-Pick disease type C. Thirty-two patients with Niemann-Pick disease type C, median age 6.9 years (1.8-33 years), underwent 64 general anesthetics for diagnostic procedures. Perianesthetic morbidity included need for tracheal reintubation, pneumonitis, hypothermia, and seizure. Therefore, Niemann-Pick disease type C-associated neurologic and visceral involvement might have anesthetic implications that neurologists and pediatricians should be aware of and consider discussing with parents, guardians, and the patient's care team when procedures requiring anesthesia are planned. Furthermore, it is important for delivery of safe anesthesia that there is communication among care team members so that all involved understand the disease manifestation spectrum.
Journal of child neurology 02/2012; · 1.59 Impact Factor
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Alfia Khaibullina,
Nicholas Kenyon,
Virginia Guptill,
Martha M Quezado,
Li Wang,
Deloris Koziol,
Robert Wesley,
Pablo R Moya,
Zhongjian Zhang,
Arjun Saha,
Anil B Mukherjee, Zenaide M N Quezado
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ABSTRACT: Infantile neuronal ceroid lipofuscinosis (INCL) is a fatal neurodegenerative disorder caused by a deficiency of palmitoyl-protein thioesterase-1 (PPT1). We have previously shown that children with INCL have increased risk of hypothermia during anesthesia and that PPT1-deficiency in mice is associated with disruption of adaptive energy metabolism, downregulation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), and mitochondrial dysfunction. Here we hypothesized that Ppt1-knockout mice, a well-studied model of INCL that shows many of the neurologic manifestations of the disease, would recapitulate the thermoregulation impairment observed in children with INCL. We also hypothesized that when exposed to cold, Ppt1-knockout mice would be unable to maintain body temperature as in mice thermogenesis requires upregulation of Pgc-1α and uncoupling protein 1 (Ucp-1) in brown adipose tissue. We found that the Ppt1-KO mice had lower basal body temperature as they aged and developed hypothermia during cold exposure. Surprisingly, this inability to maintain body temperature during cold exposure in Ppt1-KO mice was associated with an adequate upregulation of Pgc-1α and Ucp-1 but with lower levels of sympathetic neurotransmitters in brown adipose tissue. In addition, during baseline conditions, brown adipose tissue of Ppt1-KO mice had less vacuolization (lipid droplets) compared to wild-type animals. After cold stress, wild-type animals had significant decreases whereas Ppt1-KO had insignificant changes in lipid droplets compared with baseline measurements, thus suggesting that Ppt1-KO had less lipolysis in response to cold stress. These results uncover a previously unknown phenotype associated with PPT1 deficiency, that of altered thermoregulation, which is associated with impaired lipolysis and neurotransmitter release to brown adipose tissue during cold exposure. These findings suggest that INCL should be added to the list of neurodegenerative diseases that are linked to alterations in peripheral metabolic processes. In addition, extrapolating these findings clinically, impaired thermoregulation and hypothermia are potential risks in patients with INCL.
PLoS ONE 01/2012; 7(11):e48733. · 4.09 Impact Factor
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ABSTRACT: Nitric oxide synthases (NOSs) have been shown to modulate thermal hyperalgesia and mechanical hypersensitivity in inflammatory and neuropathic pain. However, little is known about the effect of NOSs on baseline function of sensory nerve fibers. Using genetic deficiency and pharmacologic inhibition of NOSs, we examined the impact of the three isoforms NOS1, NOS2, and NOS3 on baseline nocifensive behavior by measuring current vocalization threshold in response to electrical stimulation at 5, 250, 2000 Hz that preferentially stimulate C, Aδ, and Aβ fibers. In response to 5, 250 and 2000 Hz, NOS1-deficient animals had significantly higher current vocalization thresholds compared with wild-type. Genetic deficiency of NOS2 was associated with higher current vocalization thresholds in response to 5 Hz (C-fiber) stimulation. In contrast, NOS3-deficient animals had an overall weak trend toward lower current vocalization thresholds at 5 Hz and significantly lower current vocalization threshold compared with wild-type animals at 250 and 2000 Hz. Therefore, NOSs distinctively affect baseline mouse current vocalization threshold and appear to play a role on nocifensive response to electrical stimulation of sensory nerve fibers.
Nitric Oxide 12/2011; 26(2):81-8. · 3.55 Impact Factor
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ABSTRACT: Sine-wave electrical stimulation at frequencies 2000, 250, and 5Hz to respectively evaluate Aβ, Aδ, and C sensory neurons has recently been added to the armamentarium used to evaluate sensory neurons. We developed an automated nociception assay using sine-wave stimulation methodology to determine current vocalization threshold in response to 2000, 250, and 5Hz and examine the effects of sex, analgesics, and anesthetics in mice. At baseline, males had significantly higher mean current vocalization thresholds compared with female mice at 2000, 250, and 5Hz (p≤0.019). By 1h after intrathecal injections of morphine there were significant increases in current vocalization threshold percent changes from baseline that varied with doses (p=0.0001) and frequency used (p<0.0001). Specifically, with increasing doses of morphine, there were significantly greater increases in current vocalization threshold percent changes from baseline in response to 5Hz compared with 250 and 2000Hz stimulation in a significantly ordered pattern: 5Hz>250Hz (p<0.0001) and 250Hz>2000Hz (p=0.0002). Forty-five minutes after exposure, there were no effects of isoflurane on current vocalization thresholds at any frequency. Therefore, our findings suggest that this automated nociception assay using sine-wave stimulation in mice, can be valuable for measurements of the effects of sex, opioids, and anesthetics on the response to electrical stimuli that preferentially stimulate Aβ, Aδ, and C-sensory fibers in vivo. This investigation suggests the validation of this assay and supports its use to examine mechanisms of nociception in mice.
Journal of neuroscience methods 08/2011; 201(2):390-8. · 2.30 Impact Factor
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ABSTRACT: Bilateral myringotomy (BMT) is a commonly performed otolaryngologic procedure in children.
To examine the effects of intranasal dexmedetomidine, an α(2)-adrenoceptor agonist, on time-averaged pain scores, pain control, need for rescue analgesia, and agitation scores in children undergoing BMT.
We designed a trial to enroll 160 children randomized to one of four groups: two study groups, dexmedetomidine (1 or 2 μg·kg(-1)), or two control groups representing our institutional standards of practice (intranasal fentanyl-2 μg·kg(-1) or acetaminophen as needed postoperatively).
After 101 children were enrolled, patient caregivers observed that some enrollees were excessively sedated and required prolonged postanesthesia care unit (PACU) stay. This observation led to an unplanned interim analysis and early trial termination. After data were collected, severe nonnormality of pain and agitation scores necessitated a switch of the outcome to assess repeated measurements of the proportion of patients with pain, severe pain, and agitation. Demographics, time to emergence, and agitation were similar among all groups. The risk of requiring acetaminophen rescue (P < 0.0001) and proportion of patients having pain (P = 0.016) was significantly higher in one control group (rescue analgesia only) compared with fentanyl or dexmedetomidine groups. Importantly, length of stay in the PACU was significantly longer in dexmedetomidine-2 μg·kg(-1)-treated compared with dexmedetomidine-1 μg·kg(-1)-treated, fentanyl-treated, or the control group, P = 0.0037.
In this trial, we were unable to answer the original question as to the role of dexmedetomidine on time-averaged pain and agitation scores after BMT. However, our findings clearly demonstrate that in children undergoing BMT, at higher doses, dexmedetomidine significantly prolongs length of stay in the PACU.
Pediatric Anesthesia 05/2011; 21(11):1128-35. · 2.10 Impact Factor
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ABSTRACT: Dexmedetomidine, a selective α(2) adrenoreceptor agonist, has analgesic and sedative properties, minimal impact on respiratory parameters, and reportedly decreases analgesic requirements after surgery. Given its pharmacodynamic profile, dexmedetomidine might have a role for postoperative pain control in children undergoing tonsillectomy. In this study, we hypothesized that dexmedetomidine would delay and decrease opioid requirements after tonsillectomy.
In a double-blind controlled trial, participants undergoing tonsillectomy were randomized to receive one intravenous dose of fentanyl (1 μg·kg(-1) or 2 μg·kg(-1)) or dexmedetomidine (2 μg·kg(-1) or 4 μg·kg(-1)) immediately after endotracheal intubation. Primary outcomes included requirement for rescue morphine in the initial postoperative period.
One hundred and one children were enrolled. During the postoperative period, dexmedetomidine (2 and 4 μg·kg(-1) groups combined) significantly prolonged the opioid-free interval of children who underwent tonsillectomy compared with fentanyl (1 and 2 μg·kg(-1) groups combined) (P < 0.001). Children treated with dexmedetomidine 2 μg·kg(-1) vs dexmedetomidine 4 μg·kg(-1) had similar cumulative incidence curves for time to morphine rescue, whereas there was a small difference in time to first morphine rescue administration when comparing fentanyl 1 μg·kg(-1) vs fentanyl 2 μg·kg(-1). Furthermore, length of stay in the postanesthesia care unit was significantly longer for children treated with dexmedetomidine vs children treated with fentanyl (P = 0.0016).
High-dose dexmedetomidine decreases opioid requirements, prolongs the opioid-free interval after tonsillectomy, and prolongs length of stay in the postanesthesia care unit. It is conceivable that these early opioid-sparing effects could benefit patients at risk for respiratory complications early in the postoperative course after tonsillectomy (e.g., patients with obstructive sleep apnea). (ClinicalTrials.gov number, NCT00654511).
Canadian Anaesthetists? Society Journal 04/2011; 58(6):540-50. · 2.31 Impact Factor
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ABSTRACT: Previous studies suggest that the transient receptor potential vanilloid 1 (TRPV1) channel has a role in sepsis, but it is unclear whether its effect on survival and immune response is beneficial or harmful.
We studied the effects of genetic (Trpv1-knockout vs. wild-type [WT] mice) and pharmacologic disruption of TRPV1 with resiniferatoxin (an agonist) or capsazepine (an antagonist) on mortality, bacterial clearance, and cytokine expression during lipopolysaccharide or cecal ligation and puncture-induced sepsis.
After cecal ligation and puncture, genetic disruption of TRPV1 in Trpv1-knockout versus WT mice was associated with increased mortality risk (hazard ratio, 2.17; 95% CI, 1.23-3.81; P = 0.01). Furthermore, pharmacologic disruption of TRPV1 with intrathecal resiniferatoxin, compared with vehicle, increased mortality risk (hazard ratio, 1.80; 95% CI, 1.05-3.2; P = 0.03) in WT, but not in Trpv1-knockout, mice. After lipopolysaccharide, neither genetic (Trpv1 knockout) nor pharmacologic disruption of TRPV1 with resiniferatoxin had significant effect on survival compared with respective controls. In contrast, after lipopolysaccharide, pharmacologic disruption of TRPV1 with capsazepine, compared with vehicle, increased mortality risk (hazard ratio, 1.92; 95% CI, 1.02-3.61; P = 0.04) in WT animals. Furthermore, after cecal ligation and puncture, increased mortality in resiniferatoxin-treated WT animals was associated with higher blood bacterial count (P = 0.0004) and higher nitrate/nitrite concentrations and down-regulation of tumor necrosis factor α expression (P = 0.004) compared with controls.
Genetic or pharmacologic disruption of TRPV1 can affect mortality, blood bacteria clearance, and cytokine response in sepsis in patterns that may vary according to the sepsis-inducing event and the method of TRPV1 disruption.
Anesthesiology 03/2011; 114(5):1190-9. · 5.36 Impact Factor
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ABSTRACT: To quantify the incidence of adverse events associated with anesthesia given for research-driven imaging studies and to identify risk factors for those events in pediatric research subjects.
Retrospective cohort study.
National Institutes of Health Clinical Center.
Children and adolescents enrolled in clinical research protocols who required anesthesia for research-related imaging studies from January 2000 to September 2008.
Propofol sedation/anesthesia.
The occurrence of respiratory, cardiovascular, and all anesthesia-related adverse events that required intervention while receiving anesthetics for research-driven imaging studies and other noninvasive procedures.
We identified 607 children who received 1480 propofol anesthetic procedures for imaging studies. Seventy percent of anesthetics were given to subjects with severe diseases and significant disabilities (American Society of Anesthesiologists Physical Status [ASA] III). Anesthesia had a mean (SD) duration of 115 (55) minutes, and in 12.5% of procedures, an airway device was necessary. There were 98 notable respiratory, cardiovascular, and other events in 79 anesthetic procedures, a rate of 534 per 10 000 anesthetic procedures with 1 or more adverse events. There was no long-lasting morbidity or mortality. The ASA classification (odds ratio [OR], 2.92; 95% confidence interval [CI], 1.24-6.88), anesthetic effect duration (OR, 1.46; 95% CI, 1.25-1.70), and presence of airway abnormalities (OR, 4.41; 95% CI, 1.60-12.12) were independently associated with adverse events during anesthetic use.
In our clinical research sample of high-risk children who received sedation/anesthesia by an anesthesiologist, we observed a low incidence of adverse events and no long-term complications. Risk factors for adverse events included higher ASA classification, increasing anesthetic duration, and presence of airway abnormalities.
Archives of pediatrics & adolescent medicine 06/2010; 164(6):554-60. · 3.73 Impact Factor
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ABSTRACT: Neuronal ceroid lipofuscinoses (NCLs) are a group of autosomal recessive neurodegenerative diseases characterized by lysosomal accumulation of autofluorescent material in neurons and other cell types. The infantile NCL (INCL) subtype is rare (1 in >100,000 births), the most devastating of childhood subtypes, and is caused by mutations in the gene CLN1, which encodes palmitoyl-protein thioesterase-1.
To investigate the incidence of hypothermia and bradycardia during general anesthesia in patients with INCL, we conducted a case-control study to examine the perianesthetic course of patients with INCL and of controls receiving anesthesia for diagnostic studies.
Eight children with INCL (mean age 25 mo [range, 10-32] at first anesthetic) and 25 controls (mean age 44 mo [range, 18-92]) underwent 62 anesthetics for nonsurgical procedures. Patients with INCL had neurologic deficits including developmental delay, myoclonus, and visual impairment. Patients with INCL had lower baseline temperature (36.4 +/- 0.1 vs 36.8 +/- 0.1, INCL versus controls, P < 0.007), and during anesthesia, despite active warming techniques, had significantly more hypothermia (18 vs 0 episodes, P < 0.001) and sinus bradycardia (10 vs 1, P < 0.001) compared with controls. INCL diagnosis was significantly associated with temperature decreases during anesthesia (P < 0.001), whereas age, sex, and duration of anesthesia were not (P = NS).
We report that patients with INCL have lower baseline body temperature and during general anesthesia, despite rewarming interventions, are at increased risk for hypothermia and bradycardia. This suggests a previously unknown INCL phenotype, impaired thermoregulation. Therefore, when anesthetizing these children, careful monitoring and routine use of warming interventions are warranted.
Anesthesia and analgesia 08/2009; 109(2):372-8. · 3.08 Impact Factor
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ABSTRACT: We describe the case of an infant undergoing endoscopic repair of a laryngeal cleft where the combination of dexmedetomidine and propofol infusions was used as the anesthetic technique. With this regimen, endotracheal intubation was unnecessary during the perioperative period, the procedure lasted approximately 3h, and the child recovered uneventfully. Historically, the techniques used for microlaryngeal surgery involve the use of intermittent endotracheal intubation and insufflation of halogenated anesthetics to the oropharynx. Given the potential benefits of a technique that obviates the need for endotracheal intubation during microlaryngeal surgery and prevents insufflation of halogenated anesthetics in an open environment, the combination of propofol and dexmedetomidine should be considered as a viable and desirable anesthetic option for infants undergoing complex microlaryngeal surgery.
International journal of pediatric otorhinolaryngology 07/2009; 73(9):1311-2. · 0.85 Impact Factor
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ABSTRACT: Percutaneous hepatic perfusion (PHP), a regional cancer therapy, entails insertion of percutaneous catheters to isolate hepatic vasculature and enable simultaneous hepatic venous hemofiltration of high-dose chemotherapy. PHP has been shown to be safe and to benefit some patients with liver metastases.
We examined hemodynamic and metabolic changes as well as anesthetic implications during PHP in patients with metastatic liver cancer enrolled in clinical trials of escalating doses of melphalan between 2001 and 2006.
Fifty-one patients underwent 136 PHPs with general anesthesia. Diagnoses included neuroendocrine tumors, melanoma, and metastatic carcinomas. Based upon available data derived from all procedures, incorporating multiple procedures per patient, after occlusion of the inferior vena cava and during hepatic perfusion, there were decreases in mean arterial (-15.4 +/- 1 and -7.4 +/- 1 mmHg, respectively) and central venous pressure (-5.4 +/- 0.3 and -5.6 +/- 0.3 mmHg) and increases in heart rate (11 +/- 1 and 13.4 +/- 0.9 bpm) (all p < 0.0001) which resolved with completion of the procedure. During vascular isolation, patients received norepinephrine (13% of procedures), phenylephrine (70%), or both agents (11%). During hepatic perfusion with melphalan, compared to baseline, there were decreases in pH (-0.09 +/- 0.01) and bicarbonate (-3.3 +/- 0.6 mmol/L) (both p < 0.0001) and, upon completion of procedure, increases (2.6 +/- 0.4 mmol/L) in bicarbonate, compared to values during hepatic perfusion (p < 0.0001).
PHP therapy can be associated with transient but significant hemodynamic and metabolic perturbations. In order to assure patient comfort and facilitate timely diagnosis and treatment of associated hemodynamic and metabolic changes, we favor administration of general anesthesia, rather than sedation, for patients undergoing PHP.
Annals of Surgical Oncology 03/2008; 15(3):815-23. · 4.17 Impact Factor
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ABSTRACT: To investigate the role of neuronal nitric oxide synthase (NOS1) in murine polymicrobial peritonitis and sepsis.
Randomized experimental trial.
Animal research facility.
B6129S NOS1+/+ and B6;129S4 NOS-/- mice.
NOS1+/+ and NOS1-/- animals underwent cecal ligation and puncture (CLP) or sham surgery and received the NOS1 inhibitor 7-nitroindazole (7-NI) or vehicle.
After CLP, genetic deficiency and pharmacologic inhibition of NOS1 significantly increased risk of mortality [8.69 (3.27, 23.1), p<0.0001 and 1.71 (1.00, 2.92) p=0.05, hazard ratio of death (95% confidence interval) for NOS1-/- and 7-NI-treated NOS1+/+ respectively] compared with NOS1+/+ animals. In 7-NI-treated NOS1+/+ animals, there were increases (6 h) and then decreases (24 h), whereas in NOS-/- animals persistent increases in blood bacteria counts (p=0.04 for differing effects of 7-NI and NOS1-/-) were seen compared with NOS1(+/+) animals. After CLP, NOS1(-/-) had upregulation of inducible NOS and proinflammatory cytokines and greater increases in serum tumor necrosis factor-alpha and interleukin-6 levels compared with NOS1+/+ mice (all p<0.05). Following CLP, there were similar significant decreases in circulating leukocytes and lung lavage cells (p<or=0.0008) and significant increases in peritoneal lavage cells (p=0.0045) in all groups. Over 6 h and 24 h following CLP, compared with NOS1+/+, NOS-/- mice had significantly higher peritoneal cell concentrations {respectively 0.40+/-0.09 vs 0.79+/-0.15 [log(x10(4)cells/ml)] averaged over both times p=0.038}.
Deficiency and inhibition of NOS1 increases mortality, possibly by increasing proinflammatory cytokine response and impairing bacterial clearance after CLP. These data suggest that NOS1 is important for survival, bacterial clearance, and regulation of cytokine response during infection and sepsis.
Intensive Care Medicine 11/2007; 33(11):1993-2003. · 5.40 Impact Factor
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ABSTRACT: Neonatal-onset multi-system inflammatory disease (NOMID), a rare autosomal dominantly inherited disease, belongs to a growing spectrum of autoinflammatory diseases, is characterized by urticarial rash, arthropathy, and chronic aseptic meningitis, and is associated with mutations in the cold-induced autoinflammatory gene, CIAS1, the gene that encodes the protein, cryopyrin. As little is known about the anesthetic considerations of the disease, we sought to identify the main features and respective anesthetic and perioperative implications of NOMID.
We examined perianesthetic records of children with NOMID who were anesthetized for invasive diagnostic and therapeutic interventions between 2003 and 2006. In addition, we conducted an extensive literature review of the genetic, clinical, and biochemical abnormalities of the disease.
Seventeen children with NOMID (median age 8 yr, range 9 mo to 11 yr) were anesthetized for diagnostic and therapeutic procedures. All patients had neurological involvement, including increased intracranial pressure, chronic aseptic meningitis, and developmental delay; 7 had bony overgrowth, 15 ocular, and 14 otological manifestations of NOMID. Despite the complexity of the disease, the perioperative course was uncomplicated, and no serious adverse events were observed.
This study is the first to investigate the anesthetic implications of NOMID, an autoinflammatory disease associated with arthropathy, recurrent fevers, urticarial rash, and chronic aseptic meningitis. While for the pediatric anesthesiologist, the presence of fever and aseptic meningitis might make the conduct of anesthetics for elective procedures less desirable, our findings suggest that without evidence of active infection, even in the presence of fever and chronic aseptic meningitis, general and regional anesthesia may be conducted in patients with NOMID without untoward complications.
Anesthesia and analgesia 09/2007; 105(2):351-7. · 3.08 Impact Factor
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ABSTRACT: Dexmedetomidine, an alpha(2)-adrenergic agonist, decreases lipolysis and thus prevents nonshivering thermogenesis in infants. We report the case of a two-day-old neonate who received dexmedetomidine for sedation and analgesia after undergoing primary repair of bladder exstrophy. After 9 hours, the patient developed bradycardia and profound hypothermia. The bradycardia was unresponsive to anticholinergics but resolved approximately two hours after radiant heat was applied. This report highlights the potential profound impact of dexmedetomidine on thermoregulation in neonates. Dexmedetomidine impacts thermoregulation in neonates and its use warrants careful attention to the control of temperature and to the routine use of exogenous heat.
Journal of Clinical Anesthesia 07/2007; 19(4):290-2. · 1.21 Impact Factor
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ABSTRACT: In children with advanced stages of cancer, pain control remains inadequate in many patients and a solution to this problem is sorely lacking. Factors related to progression of the primary disease and side-effects of high doses of opioids, the mainstay of pain therapy, contribute to the inadequacy of pain control. In addition, few studies suggest that opioids, by inducing tolerance, having pronociceptive effects and producing hyperalgesia in some patients, can also contribute to inadequacy of pain control. Researchers have shown that N-methyl-D-aspartate (NMDA) receptor antagonists may have a role in mitigating opioid-induced tolerance and hyperalgesia in adults. However, literature on NMDA antagonists to treat cancer pain in children and adolescents is scarce. We used subanesthetic doses of ketamine to treat 11 children and adolescents who were on high doses of opioids and yet had uncontrolled cancer pain. A low-dose ketamine infusion was administered to all patients to modulate the need for rapidly escalating opioid therapy. We found that in 8 of 11 patients, ketamine infusions used as an adjuvant to opioid analgesia was associated with opioid-sparing effects and apparent improvement in pain control and in the children's ability to interact with their family. This study suggests that infusions of ketamine may offer a promising therapeutic option in the treatment of appropriately selected children and adolescents with intractable cancer pain. PERSPECTIVE: In many children with advanced stages of cancer, pain control remains inadequate. We used subanesthetic doses of ketamine to treat 11 children and adolescents who were on high doses of opioids and had uncontrolled cancer pain. In the majority of patients, ketamine appeared to improve pain control and to have an opioid-sparing effect.
Journal of Pain 07/2007; 8(6):515-21. · 4.93 Impact Factor
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ABSTRACT: Subacute combined degeneration is an acquired myelopathy caused by vitamin B12 deficiency. Therapy with B12 leads to improvement in most but to complete recovery in only a few patients. Prognostic indicators in subacute combined degeneration are unknown; therefore, predicting complete recovery of neurologic deficits is challenging.
To identify potential correlates of outcome and to generate hypotheses concerning predictors of complete resolution of neurologic deficits in subacute combined degeneration.
We searched EMBASE (1974 to October 2005), MEDLINE (1968 to October 2005), and references from identified reports. REPORTS SELECTION: Reports of patients with subacute combined degeneration containing results of magnetic resonance imaging (MRI) and description of outcome and 1 patient treated by the authors. DATA EXTRACTION, SYNTHESIS: We extracted data from 45 reports and 57 patients (36 males, 21 females; age range: 10 to 81) with a diagnosis of subacute combined degeneration, and estimated the strength of association between clinical, laboratory, and radiological factors and complete resolution of signs and symptoms.
Eight patients (14%) achieved clinical resolution and 49 (86%) improved with B12 therapy. The absence of sensory dermatomal deficit, Romberg, and Babinski signs were associated with a higher complete resolution rate. Patients with MRI lesions in < or = 7 segments and age less than 50 also appear to have higher rates of complete resolution.
B12 therapy is reported to stop progression and improve neurologic deficits in most patients with subacute combined degeneration. However, complete resolution only occurs in a small percentage of patients and appears to be associated with factors suggestive of less severe disease at the time of diagnosis.
Journal of General Internal Medicine 10/2006; 21(10):1063-8. · 2.83 Impact Factor
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ABSTRACT: Age-related changes in nociception have been extensively studied in the past decades. However, it remains unclear whether in addition to the increased incidence of chronic illness, age-related changes in nociception contribute to increased prevalence of pain in the elderly. Although a great deal of evidence suggests that nociception thresholds increase with aging, other studies yield disparate results. The aim of this investigation was to longitudinally determine the effect of aging on nociception.
The authors developed a nociception assay for mice using electrical stimuli at 2,000, 250, and 5 Hz that reportedly stimulate Abeta, Adelta, and C sensory nerve fibers, respectively. A system was designed to automate a method that elicits and detects pain-avoiding behavior in mice. Using a Latin square design, the authors measured current vocalization thresholds serially over the course of mice's life span.
For 2,000-Hz (Abeta), 250-Hz (Adelta), and 5-Hz (C) electrical stimuli, current vocalization thresholds first decreases and then increases with aging following a U-shaped pattern (P < 0.001). In addition, average current vocalization thresholds at youth and senescence are significantly higher than those at middle age for the 250-Hz (Adelta) and 5-Hz (C fiber) electrical stimulus (P < 0.05).
Using a novel and noninjurious nociception assay, the authors showed that over the life span of mice, current vocalization threshold to electrical stimuli changes in a U-shaped pattern. The findings support the notion that age-related changes in nociception are curvilinear, and to properly study and treat pain, the age of subjects should be considered.
Anesthesiology 08/2006; 105(2):360-9. · 5.36 Impact Factor
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ABSTRACT: To report the use of dexmedetomidine to facilitate rapid opioid and benzodiazepine withdrawal in children with transplanted hearts and to review the receptor physiology and pharmacodynamic impact of dexmedetomidine on the denervated heart.
Case series.
Intensive care unit at a tertiary pediatric medical center.
The series included a 6-month-old infant with pulmonary atresia who had a 3-month exposure to high-dose opioids and benzodiazepines and had undergone cardiac transplantation 4 wks before the use of dexmedetomidine and a 7-yr-old boy who had been sedated while undergoing extracorporeal membrane oxygenation for 3 wks before transplantation and started to receive dexmedetomidine 3 days after transplantation.
Administration of dexmedetomidine to facilitate the discontinuation of opioids and benzodiazepine.
Successful rapid withdrawal from opioids and benzodiazepines while maintaining hemodynamic stability.
To our knowledge, this report describes the first use of dexmedetomidine to facilitate opioid withdrawal in children with a cardiac transplant. Dexmedetomidine allowed for the preservation of satisfactory hemodynamic parameters during acute withdrawal from opioids in children with denervated hearts.
Critical Care Medicine 10/2005; 33(9):2110-2. · 6.33 Impact Factor
