Effects of dobutamine, norepinephrine, and vasopressin on cardiovascular function in anesthetized neonatal foals with induced hypotension

ArticleinAmerican Journal of Veterinary Research 67(10):1730-7 · November 2006with 34 Reads
Abstract
To determine the effects of dobutamine, norepinephrine, and vasopressin on cardiovascular function and gastric mucosal perfusion in anesthetized foals during isoflurane-induced hypotension. 6 foals that were 1 to 5 days of age. 6 foals received 3 vasoactive drugs with at least 24 hours between treatments. Treatments consisted of dobutamine (4 and 8 Sang/kg/min), norepinephrine (0.3 and 1.0 Sang/kg/min), and vasopressin (0.3 and 1.0 mU/kg/min) administered IV. Foals were maintained at a steady hypotensive state induced by a deep level of isoflurane anesthesia for 30 minutes, and baseline cardiorespiratory variables were recorded. Vasoactive drugs were administered at the low infusion rate for 15 minutes, and cardiorespiratory variables were recorded. Drugs were then administered at the high infusion rate for 15 minutes, and cardiorespiratory variables were recorded a third time. Gastric mucosal perfusion was measured by tonometry at the same time points. Dobutamine and norepinephrine administration improved cardiac index. Vascular resistance was increased by norepinephrine and vasopressin administration but decreased by dobutamine at the high infusion rate. Blood pressure was increased by all treatments but was significantly higher during the high infusion rate of norepinephrine. Oxygen delivery was significantly increased by norepinephrine and dobutamine administration; O2 consumption decreased with dobutamine. The O2 extraction ratio was decreased following norepinephrine and dobutamine treatments. The gastric to arterial CO2 gap was significantly increased during administration of vasopressin at the high infusion rate. Norepinephrine and dobutamine are better alternatives than vasopressin for restoring cardiovascular function and maintaining splanchnic circulation during isoflurane-induced hypotension in neonatal foals.
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    Full-text available
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  • Article
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    Equine neonates may suffer from a variety of diseases; perinatal asphyxia syndrome (PAS) and neonatal sepsis are particular severe, often life-threatening diseases that have the potential to affect homoeostasis of many organ systems. Regardless of the underlying disease process, some general principles apply to the treatment of any critically ill neonatal foal. Maintenance of a normal fluid, electrolyte and acid-base balance as well as cardiovascular and pulmonary function to ensure adequate perfusion and oxygen delivery to peripheral organs is one of the most important aspects of supportive care. Hypovolaemia and dehydration are addressed by administration of boluses of a balanced electrolyte solution while maintenance fluid requirements are best met using a hypotonic solution with a low sodium and a higher potassium content. If fluid therapy alone does not improve peripheral perfusion, use of inotropes and vasopressors may be indicated. Hypoxaemia can be combated by intranasal oxygen insufflation, pharmacological stimulation of the respiratory centre or mechanical ventilation. Blood transfusions may be necessary to improve the oxygen carrying capacity in certain patients. Enteral or parenteral nutrition also constitute an essential part of the treatment plan. With adequate supportive care even critically ill equine neonates can survive and develop into normal foals.
  • Article
    Background: In the horse, effects of cardiovascular-active drugs on local perfusion of the gastrointestinal tract are poorly understood. Objectives: To determine the effect of drugs commonly used to support blood pressure, on local intestinal blood flow and tissue oxygenation under isoflurane anaesthesia. Study design: In vivo randomised crossover experiment METHODS: Ten horses were anaesthetised with isoflurane. After 90 minutes of equilibration three doses (μg/kg bwt/min) of dobutamine (DOB 0.5/1/3), dopamine (DA 1/2/5), noradrenaline (NA 0.1/0.2/0.5) and phenylephrine (PHE 0.5/1/3) were infused for 15 minutes, in a randomised order, with a 45 minute washout-period. Blood flow and tissue oxygenation (sO2 ) of jejunum, colon and stomach were measured using white light remission spectrophotometry and laser doppler flowmetry; heart rate (HR), mean arterial blood pressure (MAP), cardiac output (CO) were measured and systemic vascular resistance (SVR) calculated. Results: Compared to baseline high dose dobutamine significantly increased CO, HR, MAP (p<0.001) and blood flow to the jejunum (+47 ± 26%, p = 0.001) and colon (+29 ± 15%, p<0.001) (mean ± s.d.). Dopamine (DA5) increased CO but decreased colonic blood flow (-39 ± 21% from baseline, p<0.001), as well as SVR and MAP compared to baseline (p<0.001). Noradrenaline had no significant influence on intestinal perfusion, but increased MAP and SVR from baseline (p<0.001). Phenylephrine (PHE3) caused a significant decrease in blood flow and sO2 , most profoundly at the colon compared to baseline (flow -44 ± 21%; sO2 -16 ± 3%, p<0.001), while MAP and SVR increased and CO and HR decreased (p<0.001). Main limitations: The measurement technique only allows for flow measurements in arbitrary units, which can limit comparability to other techniques. Conclusion: At the investigated doses dobutamine improved systemic and peripheral haemodynamics, while dopamine decreased MAP and peripheral perfusion. Noradrenaline increased MAP and SVR while peripheral blood flow was maintained, phenylephrine increased MAP, but reduced both local and systemic perfusion. This article is protected by copyright. All rights reserved.
  • Chapter
    The primary focus of monitoring anesthetized patients is the assessment of depth of anesthesia, cardiovascular and pulmonary consequences of the anesthetized state, and temperature. Animals that are too deeply anesthetized may suffer adverse cardiopulmonary consequences and death. Anesthetic depth is determined by: the amount of anesthetic drug(s) in the brain, the magnitude of surgical (or environmental) stimulation, and underlying conditions that have synergistic CNS depressant effects (i.e., hypothermia, hypotension). Lacrimation in horses is a sign of a light level of anesthesia. The Bispectral Index is a processed electroencephalogram that quantifies the degree of anesthetic induced cortical depression. Heart rate is an important determinant of cardiac output. Arterial blood pressure is arterial hydrostatic pressure compared with atmospheric pressure. Direct measurement of arterial blood pressure, via an arterial catheter, is more continuous and less variable than using indirect methods. Central venous pressure (CVP) is the luminal pressure of the intrathoracic vena cava.
  • Chapter
    Equine anesthesia has always been associated with greater patient risk compared to other common domestic species. Understanding of the unique factors associated with equine anesthesia compared to other species is the first step in improving patient safety. Surgical tables and hoisting mechanisms must be designed specifically for equine or large animal patients. Anatomic variation complicates cardiopulmonary resuscitation. An equine neonate or older foal can be managed similar to a canine but adult equine ribs are narrow and impossible to separate by hand if open chest cardiac compressions are required. Inducing recumbency in horses from the standing position can be dangerous. A pregnant mare presenting for an emergency procedure requiring general anesthesia has several physiologic differences that challenge the anesthetist. A discussion involving fluid therapy in horses under general anesthesia can be controversial. The true challenge of equine anesthesia compared to other domestic species is safely returning the patient to the standing position without injury.
  • Chapter
    Adrenergic agents are drugs that act on the sympathetic nervous system (SNS) and as such are widely used in veterinary anesthesia for the management of cardiorespiratory function. Adrenergic agents that are agonists at α1-, β1- and β2-receptors are also classified as sympathomimetics because they cause stimulation. This chapter discusses naturally occurring catecholamines, followed by synthetic catecholamines and then other non-catecholamine synthetic adrenergic agents. Epinephrine acts non-selectively and directly as an agonist at all of the adrenergic receptors. Clenbuterol, albuterol, and terbutaline are predominantly used for the management of bronchospasm in people with asthma. Ephedrine is used in the management of hypotension during anesthesia. Phenylephrine is a direct-acting sympathomimetic amine with potent α1 -adrenergic receptor agonist effects and therefore it is often referred to as 'vasopressor'.
  • Chapter
    Adjunctive drugs can be broadly described as drugs which fall outside common clinical use but may provide a benefit beyond that of more commonly used drugs or are less readily characterized because they play a supportive role in the provision of anesthesia and analgesia. The chapter is divided into non-analgesic and analgesic adjuncts. Dantrolene is a peripherally acting muscle relaxant, producing skeletal muscle relaxation through ryanodine receptor antagonism. Maropitant is a neurokinin (NK1) receptor antagonist licensed as an antiemetic in dogs and cats. Methocarbamol is a centrally acting muscle relaxant that selectively inhibits spinal and supraspinal polysynaptic reflexes through its action on interneurons, without direct effects on skeletal muscle. The analgesic agent tapentadol was designed with the aims of combining μ opioid receptor agonism and norepinephrine reuptake inhibition without dependency on generating active metabolites, as is the case with tramadol.
  • Chapter
    This chapter discusses the anesthetic management of horses with colic using a combination of the authors' experiences and published information. Colic related to gastrointestinal (GI) disease is one of the most significant causes of morbidity and mortality in horses, with a reported incidence from 3.5 to 10.6 cases per 100 horses per year. Disruption of GI mucosal barriers by ischemia leads to movement of lipopolysaccharide (LPS) into the peritoneal cavity and eventually uptake into the systemic circulation. Preanesthetic evaluation and preparation are important factors that influence successful outcome in horses with colic. Many anesthetic agent combinations and dose rates are used to anesthetize healthy horses. Anesthetic care goes beyond the simple administration of drugs and is an important component of preventing physiological abnormalities that may impact on outcome. All the complications that occur during recovery from anesthesia in healthy horses occur in horses recovering from colic surgery.
  • Article
    The authors review the physiological specialities of the anesthesia of neonatal and young foals and summarize the techniques which can be used for sedation, induction and maintenance of general anesthesia at this age. They discuss the required intraoperative monitoring and fluid therapy, furthermore, the most frequent perioperative complications and their therapy.
  • Article
    The authors review the physiological specialities of the anesthesia of neonatal and young foals and summarize the techniques which can be used for sedation, induction and maintenance of general anesthesia at this age. They discuss the required intraoperative monitoring and fluid therapy, furthermore, the most frequent perioperative complications and their therapy.
  • Article
    Sepsis is a major cause of death in neonatal foals and, in recent years, significant progress in the understanding of the underlying pathophysiology has been made. To achieve a successful outcome, early diagnosis and treatment focusing on supporting vital functions and neutralising the effects of the causative organisms are essential. The pharmacokinetics of many drugs differ in neonatal foals and more information for appropriate dosing of antimicrobial and anti-inflammatory drugs for neonatal foals is now available to guide clinicians in choosing the best dosages. Prevention remains difficult and focuses on early recognition while prophylactic use of antimicrobials is discouraged.
  • Chapter
    This chapter begins with a discussion on the unique aspects of foal pharmacology. Neonatal foal physiology is unique, and there exist important physiological differences between foals and mature horses that have clinical implications in terms of drug absorption, distribution, metabolism, and/or elimination. The chapter discusses some generalized observations and recommendations regarding pharmacodynamics and pharmacokinetics in foals. It further talks about the clinical pharmacology for neonatal diseases. Neonatal foals are susceptible to a number of gastrointestinal disorders, including enterocolitis and colic. Ulcer prophylaxis in neonatal foals currently is controversial in equine neonatology, because of concerns of an increased susceptibility to bacterial enteric infections associated with the loss of gastric acidity. Bacterial pneumonia is the most common respiratory disease in foals. The chapter concludes with a discussion on the treatment of hypoventilation in neonatal foals and seizure control.
  • Chapter
    In physiological terms, trauma is a combination of severe tissue injury, hemorrhage, and inflammation. In this chapter, anesthetic and analgesic options to be used in patients with severe traumatic injury are discussed. All anesthetic agents cause some degree of cardiovascular and respiratory depression. Furthermore, anesthetic drugs will blunt sympathetic drive and inhibit physiological autoregulatory mechanisms that maintain adequate blood pressure and cardiac output (CO) in trauma victims. Trauma patients present with a vast array of physiological derangements that require specific care. For discussion, trauma patients are divided into head trauma, thoracic/abdominal trauma, and extremity orthopedic trauma. Pain control should be an integral part of the overall treatment plan for the trauma patient. When a patient has experienced severe trauma, the clinician should assume that the condition is extremely painful and provide appropriate treatment. Analgesic treatment in trauma represents a multistage approach involving pain assessment, intervention, and repeated re-evaluation.
  • Article
    Sepsis and septic shock represent a major cause of morbidity and mortality in equine neonates and in all species. Early recognition of the condition is important, but definitive examination and laboratory variables to predict equine neonatal sepsis are lacking. Early and aggressive treatment should include broad-spectrum antimicrobial coverage, source control, and hemodynamic support. Field practitioners and intensive care clinicians work together in the management of this condition because the recognition and initial treatment should begin as early as possible.
  • Article
    Advanced hemodynamic monitoring consisting of cardiac output monitoring and/or perfusion monitoring is reserved for the most complicated patients and for research. For serial monitoring of an individual horse, the cardiac output in liters per minute is the appropriate measurement. In the clinical patient, the ideal method of measuring cardiac output would be non-invasive, quick to set up, accurate, provide continuous real-time data, and require little or no expertise to operate. In foals, lithium dilution and the Bullet ultrasound method appear to be the most practical methods that have shown reasonably good accuracy in validation studies. Cardiac output and the derived hemodynamic parameters give very useful information about global hemodynamics. Tissue perfusion monitoring is likely to become an integral part of equine critical care in the future. Advanced hemodynamic monitoring has a place in complicated cases to guide fluid therapy and inotropic and pressor support.
  • Article
    Fluids are most often administered to horses in an effort to restore tissue perfusion and oxygen delivery and often in emergency situations. Monitoring begins with careful clinical assessment; results from laboratory tests and monitoring equipment provide additional information that enable quantification of clinical findings. The measurement of packed cell volume (PCV) and total solids (TS) concentration is simple, quick, and inexpensive. Qualitative assessment of urine production based on micturition frequency and the subjective volume of urine in the stall is sufficient in many adult horse cases. Urine specific gravity has been used by some clinicians to assess the adequacy of fluid therapy. Electrolyte concentrations should be carefully monitored during fluid therapy of more than a few days duration. Finally, it is important to recognize that most monitoring techniques assess global perfusion, which might not reveal perfusion deficits of individual tissue beds.
  • Article
    Full-text available
    Objetivou-se avaliar a eficiência do tratamento da hipotensão arterial com eletroacupuntura comparativamente à dobutamina em equinos. Foram avaliados seis cavalos adultos, saudáveis, mantidos em anestesia inalatória, com isofluorano, em ventilação mecânica. Após a estabilização da anestesia, foi induzida hipotensão arterial, através do incremento da concentração do isofluorano, iniciando-se um dos tratamentos: DOB: dobutamina (1,5µg kg-1 min-1, infusão contínua intravenosa); EA: estímulo elétrico no acuponto pericárdio 6 (PC6), bilateralmente; SHAM: estímulo elétrico em ponto falso de acupuntura. Foram mensurados: frequência cardíaca (FC), pressão arterial média (PAM), temperatura retal (T), concentração final expirada de isofluorano (ETiso), variáveis hemogasométricas, concentração sérica de aspartato aminotransferase (AST) e creatina fosfoquinase (CK), tempo e qualidade da recuperação pós-anestésica. Houve incremento na PAM de 50%, 36,6% e 7,5% nos tratamentos DOB, EA e SHAM, respectivamente. Não houve diferença entre os grupos nas variáveis hemogasométricas, FC, T, ETiso, CK, AST, tempo e qualidade de recuperação pós-anestésica. Conclui-se que o tratamento com dobutamina foi mais efetivo para o tratamento da hipotensão em cavalos sob anestesia inalatória quando comparado ao estímulo elétrico do acuponto PC6 ou ponto falso de acupuntura.
  • Article
    One of the fundamental skills required for practicing evidence-based medicine is the development of a well-built clinical question, which specifies the patient group or problem, intervention, and outcome of interest. For this purpose, various "levels of evidence" have been developed in the human literature, which rank the validity of evidence. Our established conclusions and advice are thus supported by specific "grades of recommendations," which are intended to give an indication of the "strength" of a clinical recommendation. This article was compiled with these principles in mind.
  • Article
    Measurement of pH of the stomach wall (gastric intramural pH) by the tonometric method has been utilized both experimentally and clinically as an indicator of the capability of the stomach to extract and utilize oxygen. As such, it serves as a metabolic marker of acute perfusion failure (circulatory shock). More recently, researchers have found that increases in the PCO2 accounted for the decline in pH; this was documented in tissues other than the stomach wall, including the esophageal and sublingual mucosa. In this review, tissue PCO2 is identified as a universal indicator of impaired perfusion and contrasted with conventional hemodynamic and metabolic markers of perfusion failure.
  • Article
    Objectives: To compare in the same patient with septic shock, respective effects of epinephrine, norepinephrine, and the combination of norepinephrine and dobutamine (5 [micro sign]g/kg/min) on systemic hemodynamic parameters and gastric mucosal perfusion using gastric tonometry and laser-Doppler flowmetry techniques. Design: Prospective, controlled, randomized, crossover study. Setting: University hospital intensive care unit. Patients: Twelve patients with septic shock. Interventions: Each patient received in a random succession epinephrine, norepinephrine, and norepinephrine plus dobutamine. Dosages of epinephrine and norepinephrine were adjusted to achieve a mean arterial pressure between 70 and 80 mm Hg. A laser-Doppler probe and a tonometer were introduced into the gastric lumen. Measurements and Main Results: The increase in gastric mucosal perfusion detected by laser-Doppler flowmetry was higher with epinephrine and the combination of norepinephrine and dobutamine than with norepinephrine alone (p < .05). In addition, the ratio of gastric mucosal perfusion (local oxygen delivery) to systemic oxygen delivery was increased after norepinephrine plus dobutamine as compared with norepinephrine alone and epinephrine (p < .05). Although values of intramucosal pH and gastroarterial PCO2 tended to be higher with norepinephrine plus dobutamine compared with those obtained with norepinephrine and epinephrine, differences were not statistically significant. Conclusions: For the same mean arterial pressure in patients with septic shock, our study showed that administration of epinephrine increased gastric mucosal perfusion more than norepinephrine administration alone. Addition of dobutamine (5 [micro sign]g/kg/min) to norepinephrine improved gastric mucosal perfusion. This result could be explained by a vasodilating effect of dobutamine on gastric mucosal microcirculation. (Crit Care Med 1999; 27:893-900)
  • Article
    Objective: To compare the partial CO2 rebreathing method (non-invasive cardiac output [NICO]) and the lithium dilution method (lithium dilution cardiac output [LiDCO]) for cardiac output (CO) measurement in anesthetized dogs.Design: Prospective study.Setting: College of Veterinary Medicine, University of Florida.Animals: Six adult dogs (weight range 22–25.4 kg).Interventions: All animals were instrumented for CO determinations using the LiDCO and NICO methods. Direct blood pressure, heart rate, arterial blood gases, end-tidal isoflurane (ETI), and CO2 concentrations were monitored throughout the study. CO was manipulated with dobutamine and isoflurane to allow for intermediate, low, and high CO determinations in that order using LiDCO and NICO.Measurements and main results: A 1.5% ETI produced the intermediate rate of CO, a constant-rate infusion of dobutamine (1–4 μg/kg/min) and 1.1% ETI, the highest rate, and 2.5–3% ETI, the lowest rate. Measurements were obtained in duplicate or triplicate for the LiDCO and continuously for the NICO method after achieving a stable hemodynamic plane for at least 15 minutes at each level of CO, allowing 5 minutes between measurements. Forty-seven comparisons were determined. The correlation coefficient (r) between the 2 methods was 0.888 for all determinations. The mean LiDCO and NICO from 47 measurements were 155.9±78.7 mL/kg/min (range, 49.6–303.2) and 146.6±62.9 mL/kg/min (50–290.3), respectively. The bias between LiDCO and NICO estimations was 9.3 (−60.7 to +79.4) mL/kg/min (mean and 95% confidence interval). The mean (mL/kg/min) of the differences of LiDCO–NICO was 1.11 × NICO. The relative error was 2.4±24.7%. As CO increased, the relative difference between the methods also increased.Conclusions: The NICO is a viable non-invasive method for CO determination in the dog and compares well with the LiDCO.
  • Article
    Dobutamine was infused (1.7 μg/kg/minute) into 200 anesthetized horses as treatment for hypotension. The horses had been premedicated with xylazine, and anesthesia was induced with guaifenesin and ketamine and maintained with halothane. One hundred fifty-seven horses (79%) responded with an average increase in systolic blood pressure of at least 10 mm Hg within 10 minutes. A cardiac arrhythmia developed in 56 horses (28%) after dobutamine administration: 34 with sinus bradycardia, 18 with atrioventricular block, 2 with premature atrial contractions, and 2 with atrioventricular dissociation. Dobutamine intravenous infusion was effective treatment for hypotension in horses anesthetized with halothane.
  • Article
    Full-text available
    Objectives: To study the effect of continuous infusion of vasopressin on the splanchnic circulation in patients with severe septic shock. Methods: Prospective clinical study. ICU in a teaching hospital. Eleven consecutive patients with documented septic shock who remained hypotensive despite norepinephrine infusion at a rate ≥0.2μ g/kg/min. Insertion of a gastric tonometry catheter, and continuous infusion of vasopressin 0.04 units/min during 4 hours. Results: Difference between gastric and arterial CO2 partial pressure (P[g-a]CO2 gap), mean arterial pressure, and cardiac index were recorded at baseline and after 15 minutes, 30 minutes, 60 minutes, 120 minutes, and 240 minutes. The median P[g-a]CO2 gap increased from 5 mm Hg at baseline to 19 mm Hg after 4 hours (p = .022). Mean arterial pressure increased from 61 ± 13 mm Hg at baseline to 68 ± 9mm Hg after 4 hours (p = .055). No significant changes in cardiac index were noted. Conclusions: In norepinephrine-dependent patients in septic shock, continuous infusion of low-dose vasopressin results in a significant increase of the P[g-a]CO2 gap compatible with gastrointestinal hypoperfusion.
  • Article
    Physiologic studies in dogs have been performed with an intravascular flow/diameter sensor which can be introduced directly into the aorta or its branch vessels through a percutaneous radiologic catheter. These studies have focused upon attempts to devise a clinically practical means to protect the small intestine from radiation damage during therapy of abdominal and pelvic malignant tumors. The effects on superior mesenteric, renal, and lower extremity blood flows of controlled infusions of Pitressin given directly into the superior mesenteric artery or into a peripheral vein have been measured. In addition, using these regional flow measurements and arteriovenous differences in oxygen content, regional tissue oxygen extraction rates during Pitressin infusions have also been estimated. The data show that intravenous Pitressin at an infusion rate of 0.0124 U/kg/min may be almost as effective as Pitressin given directly into the superior mesenteric artery in lowering superior mesenteric blood flow (40%-70% reduction for intravenous, 50%-70% for direct arterial infusions) and intestinal oxygen extraction (20%-40% reduction for intravenous, 40%-50% for direct arterial infusions). The effects of Pitressin at similar dose rates on the kidney and the lower extremity are less reproducible, and it is possible that relatively selective radiation protection of the intestine using systemic (intravenous) infusions of Pitressin during abdominopelvic radiotherapy might be achievable.
  • Article
    The direct effects of vasopressin on the resistance and capacitance properties of the pulmonary and systemic vasculature were studied in nine aneural dogs on systemic and pulmonary bypass. The systemic and pulmonary pressure-flow, the systemic and pulmonary arterial pressure-volume, and the systemic and pulmonary venous pressure-volume relationships were determined for five levels of infused vasopressin. Vasopressin levels of approximately 10, 30, 150, 300, and 500 pg/ml were achieved by intravenous infusions. Samples of venous blood were drawn before and after each set of pressure-flow and pressure-volume relationships for the determination of vasopressin level by radioimmunoassay. A linear relationship was found between vasopressin level and systemic vascular resistance. Systemic vascular resistance increased 0.072 +/- 0.011 mmHg.kg.min.ml-1 for a change in vasopressin level of 100 pg/ml. Vasopressin did not affect pulmonary vascular resistance or any vascular compliance. High doses of infused arginine vasopressin were necessary to elicit substantial vasoconstriction.
  • Article
    These experiments were designed to investigate whether a reflex arising from ventricular receptors is capable of stimulating vasopressin secretion during hemorrhage. Three groups of conscious dogs (sham operated, cardiac denervated, and ventricular denervated) were hemorrhaged slowly until 30 ml blood/kg body wt had been removed. Hemorrhage produced comparable decreases in stroke volume, central venous pressure, and left atrial pressure in each group of dogs but produced a different pattern of heart rate response in each group. Plasma vasopressin concentrations before hemorrhage did not differ in the three groups of dogs. In sham-operated dogs plasma vasopressin increased from a control level of 2.4 +/- 0.3 to 6.2 +/- 1.7, 200.0 +/- 65.4, and 991.3 +/- 220.9 pg/ml after 10, 20, and 30 ml/kg of blood had been removed, respectively. In contrast, plasma vasopressin did not increase in either cardiac-denervated or ventricular-denervated dogs after 10 ml/kg of blood had been removed, and the increases in circulating vasopressin after 20 and 30 ml/kg hemorrhage were markedly attenuated by cardiac denervation and by ventricular denervation. The magnitude of the increase in plasma vasopressin in the cardiac-denervated and ventricular-denervated dogs did not differ significantly at comparable levels of hemorrhage. The results are consistent with the possibility that a reflex initiated by ventricular receptors is primarily responsible for stimulating the secretion of vasopressin during hemorrhage in conscious dogs.
  • Article
    Cardiopulmonary function was studied in 10 full-term healthy foals from birth to 14 days of age. Systemic and pulmonary haemodynamics were recorded in lateral recumbency via indwelling aortic and pulmonary artery catheters. Mean body weight increased from 45.4 +/- 2.4 kg on Day 1 to 70.6 +/- 6.1 kg on Day 14. All foals had a continuous murmur of patent ductus arteriosus for 3-6 days. From Day 1 (12 h old) to Day 14, heart rate increased (89 +/- 4 to 95 +/- 5/min), mean aortic pressure increased (87.7 +/- 1.9 to 100.3 +/- 3.2 mmHg), mean pulmonary artery pressure decreased (38.6 +/- 4.6 to 27.4 +/- 3.0 mmHg), mean right atrial pressure was unchanged (4.5 +/- 0.5 to 4.6 +/- 0.9 mmHg), mean pulmonary artery wedge pressure was unchanged (7.6 +/- 0.9 mmHg to 8.1 +/- 0.7 mmHg), cardiac output increased (8.03 +/- 0.59 to 15.88 +/- 1.90 l/min), cardiac index increased (180.5 +/- 10.3 to 222.1 +/- 21.6 ml/kg/min), stroke volume increased (90.4 +/- 5.7 to 164.2 +/- 25.9 ml), stroke volume index was unchanged (2.04 +/- 0.10 to 2.30 +/- 0.35 ml/kg), pulmonary vascular resistance decreased (314 +/- 39 to 104 +/- 21 aru), systemic vascular resistance decreased (858 +/- 70 to 497 +/- 87 aru), and pulmonary/systemic resistance ratio decreased (38 +/- 6 to 21 +/- 5%). All changes were gradual, although pulmonary artery pressure and pulmonary vascular resistance decreased rapidly in the first 24 h. Catheters were well tolerated over several days, indicating their feasibility for studying cardiovascular function in full-term or premature equine neonates.
  • Article
    Arginine vasopressin (AVP) is used to treat esophageal variceal hemorrhage but has the drawbacks of rebleeding and reported coronary insufficiencies. In conscious dogs (n = 23) we compared AVP and an analog, triglycyl desamino lysine vasopressin (TDLVP), for arterial pressor responses and changes in regional blood flow. Dogs were infused with saline (n = 5), AVP (n = 7) or TDLVP (n = 7), and blood flow was measured with microspheres during control, infusion and postinfusion in 46 tissue sections including pieces of the esophagus, stomach, liver, kidney, spleen, heart, skin, muscle and brain. TDLVP (1.0 micrograms/kg/min) and AVP (0.025 micrograms/kg/min) produced a similar mean arterial pressure increase of 23 mm Hg and a heart rate decrease of 38 beats/min. TDLVP sustained the increase in mean arterial pressure and reduction in heart rate at 30 min postinfusion whereas AVP did not. Neither AVP nor TDLVP showed a reduction in brain, kidney or liver flow; however, both produced reductions (73 and 61%, respectively, P less than .01) in mucosal-esophageal flow. Only TDLVP reduced mucosal-fundus blood flow (P less than .01). Endocardial flow was reduced (27%) in both TDLVP and AVP groups; however, heart rate also decreased during this time and a linear correlation between these two measurements yielded a value for r2 of 0.83. Thus, TDLVP offers a therapeutic alternative to AVP in treating gastroesophageal varices due to its longer duration of action as represented by the sustained reduction in esophageal and mucosal-fundus flow.
  • Article
    This study compares the effect of arginine-vasopressin with phenylephrine on arterial pressure, heart rate, and renal sympathetic nerve activity in conscious rabbits with and without functional arterial baroreflexes and in rabbits with lesions of the area postrema. In intact rabbits, progressive infusions of arginine-vasopressin result in large decreases in renal sympathetic nerve activity and heart rate for a given increase in blood pressure as compared to progressive infusions of phenylephrine. In sinoaortic-denervated rabbits, the responses of arterial pressure on heart rate and renal sympathetic nerve activity to both arginine-vasopressin and phenylephrine are markedly attenuated, indicating the necessity for afferent baroreceptor activity in this response. This observation indicates that arginine-vasopressin is acting centrally to enhance the baroreflex. A central site of action of circulating vasopressin may be the area postrema, since it is the only circumventricular organ in the hindbrain. Lesioning the region of the area postrema resulted in a normalization of the responses evoked with arginine-vasopressin and phenylephrine. There was no difference in the phenylephrine responses of arterial pressure on renal sympathetic nerve activity or heart rate in area postrema-lesioned animals, compared to control rabbits. Therefore, we conclude that the area postrema or its surrounding tissue is either a site of action of circulating arginine-vasopressin or contains fibers of passage from another site where arginine-vasopressin acts to enhance baroreflex activity.
  • Article
    Although we are just beginning to appreciate the potential role that arginine vasopressin (AVP) could play in the normal regulation of arterial pressure, a number of points appear already relatively well established. There is now little doubt that AVP can exert significant vasoconstrictor actions at physiological plasma concentrations, although in normal states, AVP-induced elevations of total peripheral resistance do not raise arterial pressure because of strong reflex suppression of cardiac output. It is also clear that AVP can be released in sufficient amounts in hypovolemic states to contribute significantly to the normalization of arterial pressure by direct vasoconstriction. The interaction of AVP with autonomic reflex pathways and the enhancement of baroreceptor reflex gain appear to be an important way in which AVP can also contribute to the short-term stabilization of pressure. Finally, the rapid reflex suppression of AVP and the withdrawal of antidiuretic actions in response to volume loading may serve as another mechanism whereby AVP participates in arterial pressure stabilization.
  • Article
    The possibility that vasopressin plays a role in cardiovascular control arouses increasing interest. We studied in unanesthetized dogs the hemodynamic consequences of 1-hour vasopressin infusions that modified plasma concentrations over a range similar to that found in physiological situations. We also examined the cardiovascular events following the stimulation of endogenous vasopressin release by an increase in plasma osmolality. In dogs with baroreceptor reflexes intact, vasopressin infusions which increased plasma vasopressin concentration by 2-20 fmol/ml did not affect mean arterial pressure. However, they significantly decreased cardiac ouput (measured by an electromagnetic flowmeter) and increased total peripheral resistance. After baroreceptor denervation, vasopressin infusion rates as low as 40 fmol/kg per min (0.017 microU/kg per min) led to an increase in mean arterial pressure. Cardiac output was unaffected until much higher infusion rates were used. Changes in total peripheral resistance were very similar to those calculated in dogs with intact baroreceptors. The release of vasopressin following infusions of hypertonic solutions either intravenously or into a carotid artery induced detectable hemodynamic changes which appeared in many respects similar to those following low infusion rates of vasopressin. We conclude that physiological plasma concentrations of vasopressin have hemodynamic effects even though they do not normally modify arterial pressure, presumably because of some particular interaction of vasopressin with the baroreceptor reflex.
  • Article
    1. The effects of vasopressin and deamino-8-D-arginine vasopressin (DDAVP, desmopressin) were studied in artery rings (0.8-1 mm in external diameter) obtained from portions of human omentum during the course of abdominal operations (27 patients). 2. In arterial rings under resting tension, vasopressin produced concentration-dependent, endothelium-independent contractions with an EC50 of 0.59 +/- 0.12 nM. The V1 antagonist d(CH2)5Tyr(Me)AVP (1 microM) and the mixed V1-V2 antagonist desGly-d(CH2)5D-Tyr(Et)ValAVP (0.01 microM) displaced the control curve to vasopressin to the right in a parallel manner without differences in the maximal responses. In the presence of indomethacin (1 microM) the contractile response to vasopressin was significantly increased (P < 0.01). 3. In precontracted arterial rings, previously treated with the V1 antagonist, d(CH2)5Tyr(Me)AVP (1 microM), vasopressin produced endothelium-dependent relaxation. This relaxation was reduced significantly (P < 0.05) by indomethacin (1 microM) and unaffected by the V1-V2 receptor antagonist desGly-d(CH2)5D-Tyr(Et)ValAVP (1 microM) or by NG-nitro-L-arginine methyl ester (L-NAME, 0.1 mM). 4. The selective V2 receptor agonist, DDAVP, caused endothelium-independent, concentration-dependent relaxations in precontracted arterial rings that were inhibited by the mixed V1-V2 receptor antagonist, but not by the V1 receptor antagonist or by pretreatment with indomethacin or L-NAME. 5. Results from this study suggest that vasopressin is primarily a constrictor of human mesenteric arteries by V1 receptor stimulation; vasopressin causes dilatation only during V1 receptor blockade. The relaxation appears to be mediated by the release of vasodilator prostaglandins from the endothelial cell layer and is independent of V2 receptor stimulation or release of nitric oxide. In contrast, the relaxation induced by DDAVP is largely dependent on stimulation of V2 receptors.
  • Article
    The bolus injection of vasopressin into the vertebral artery produced a dose-dependent vasodilation in the major cerebral arteries, detected angiographically, while it elicited a decrease in vertebral blood flow. One nanomol of vasopressin was the optimal dose for producing maximal vasodilation. The basilar, posterior communicating, and internal carotid arteries showed the most dilatation, followed by the middle cerebral, the intracranial portion of the vertebral artery and the anterior spinal artery. The extracranial portion of the vertebral artery was less sensitive to vasopressin. The vasodilation was inhibited by a V1-antagonist and NG-monomethyl-L-arginine. These results suggest that the arteries of the circle of Willis at the base of the brain are more sensitive to nitric oxide release induced by vasopressin compared with other intracranial and extracranial arteries.
  • Article
    The objective of this article is to review splanchnic tonometry. The English literature, involving both animal and human studies, was used for review, with emphasis on papers on physiological and methodological principles and clinical applications. Tonometry involves the measurement of intraluminal PCO2 as a measure of mucosal PCO2 in the gastrointestinal tract via a catheter in, for instance, stomach or sigmoid colon, and the calculation, with help of the blood bicarbonate content and the Henderson-Hasselbalch equation, of the mucosal pH (pHi). The latter is considered as a relatively simple index of the adequacy of mucosal blood flow. Concerning methodology, it is still unclear whether acid secretion should be inhibited for proper assessment of PCO2 in the stomach. Buffering of bicarbonate by gastric acid may elevate the intraluminal PCO2 independently from mucosal PCO2, thereby confounding pHi as a measure of perfusion adequacy. This can be prevented by inhibition of acid secretion. Authors have raised doubts whether the composite variable pHi is of additive value to the acid-base status of arterial blood, so that it is unclear whether a subnormal pHi is a specific and sensitive indicator of mucosal ischemia, as suggested by others on the basis of a decline in the pHi along the gastrointestinal tract in animals subjected to vascular occlusion or circulatory shock. Moreover, tissue PCO2 depends on the PCO2 of supplying blood. Conversely, the bicarbonate concentration in ischemic mucosa may not equal that in arterial blood. Taken together, an elevated tonometer fluid arterial blood PCO2-gradient might be a more sensitive and specific indicator of mucosal ischemia than a decrease in the pHi, analogous to an increase in tissue PCO2 and widening of the venoarterial PCO2 gradient during various types of hypoperfusion, in animals and humans. Although splanchnic ischemia is an early event in shock, the sensitivity and specificity of this index for mucosal ischemia and its clinical value, relative to that of the pHi, have not been formally evaluated yet. Nevertheless, the pHi has been suggested to be of predictive value for gastrointestinal complications, multiple organ failure, success or failure of weaning from mechanical ventilation, and outcome in critically ill patients. Tonometry may be a useful monitoring technique to guide treatment and to improve survival. Splanchnic tonometry is a relatively simple, noninvasive, and thereby promising technique to monitor the critically ill. However, some aspects need further evaluation before the technique can be advocated for routine use.
  • Article
    A prospective study was conducted to describe the causes of and farm management factors associated with disease and death in a population of foals in Texas. Data from 2,468 foals at 167 farms were provided by veterinarians for all 12 months during 1991. Among 2,468 foals, 116 deaths were reported (4.7%). Pneumonia was the most commonly reported cause of death, followed by septicemia. When considered as a group, musculoskeletal disorders (traumatic, infectious, or deforming problems) represented the most common cause of all reported deaths. Daily risk of death was greatest during the first 7 days of life, and decreased with age. Risk and frequency of causes of death varied by age. Crude incident morbidity during the year was 27.4% (677/2,468). Respiratory disease was the most common cause of incident disease in the study population, followed by diarrhea. Risk of disease was greatest among < or = 7 days old, and decreased with age. Crude rate of incident of diarrhea was significantly lower among farms where foals were born on pasture, compared with that at farms where foals were born in stalls. The practice of assessing passive immunity was significantly associated with decreased morbidity from septicemia and pneumonia.
  • Article
    To determine the value of tonometrically measured gastric intramucosal pH (pHi) and accepted indices of systemic oxygenation in predicting multiorgan dysfunction syndrome (MODS) and death in critically ill patients with sepsis. Prospective, noninterventional study. Multidisciplinary ICU of a tertiary care, teaching hospital. Thirty critically ill ventilated patients with pulmonary artery catheters and nasogastric tonometers in place. The pHi, arterial lactate concentration, arterial and mixed venous pH, APACHE II score, and oxygen-derived variables, including oxygen delivery (Do2) and oxygen consumption (Vo2) were determined within 24 h of the onset of sepsis. The patients were then followed until death or discharge from the ICU. The development of organ system dysfunction during the ICU stay was recorded. Fifteen patients developed MODS of whom 12 died. An additional three patients died. The pHi and arterial and mixed venous pH were significantly lower in those patients who developed MODS and in those patients who died. The Vo2 and Do2, however, were higher in these patients. Using stepwise discriminant analysis, only the pHi contributed to the prediction of both MODS and death. In patients with sepsis, indices of tissue oxygenation are better predictors of outcome than the hemodynamic and oxygen-derived variables obtained by invasive hemodynamic monitoring. These indices should be used to direct therapy.
  • Article
    To provide a succinct overview of current notions regarding sepsis-induced alterations in mesenteric perfusion and oxygen transport. Selected English-language articles dealing with mesenteric perfusion and gut mucosal function during sepsis or endotoxicosis in experimental animals or man. The review emphasizes findings obtained using a well-characterized porcine model of acute, resuscitated endotoxicosis. Other experimental and clinical studies are discussed as well. Total hepatosplanchnic perfusion and oxygen uptake are increased in most patients with compensated sepsis. No data are currently available from clinical studies regarding the effect of sepsis on mesenteric perfusion per se. Data are unavailable regarding either total hepatosplanchnic or mesenteric blood flow in patients with decompensated sepsis (i.e., septic shock). Therefore, current ideas regarding mesenteric perfusion in sepsis derive primarily from studies using animal models. In a normodynamic porcine endotoxicosis model, mesenteric perfusion and oxygen delivery (DO2) are markedly decreased. The changes in flow and DO2 are accompanied by intestinal mucosal acidosis and increased permeability to hydrophilic solutes, suggesting that these latter phenomena are a consequence of lipopolysaccharide-induced mesenteric hypoperfusion. This idea is supported by the observation that maintenance of normal mesenteric blood flow ameliorates gut mucosal acidosis and hyperpermeability in endotoxic pigs. However, because transmesenteric oxygen consumption is unchanged in endotoxic pigs, the precise mechanistic relationship between hypoperfusion and altered barrier function remains puzzling. Mesenteric hypoperfusion may be an important factor leading to alterations in gut epithelial permeability in endotoxicosis and sepsis.
  • Article
    1. The isometric response to arginine-vasopressin (10(-10)-10(-7)M) was studied in 2 mm long rabbit arterial segments isolated from several vascular beds (cutaneous, pial, renal, coronary, muscular, mesenteric and pulmonary). 2. Vasopressin induced contraction in central ear (cutaneous), basilar (pial), renal, coronary and saphenous (muscular) arteries, but had no effect in mesenteric and pulmonary arteries; the order of potency for the contraction was: ear > basilar > renal > coronary > saphenous arteries. 3. Treatment with the blocker of nitric oxide synthesis NG-nitro-L-arginine methyl ester (L-NAME; 10(-6)-10(-4) M) increased significantly (P < 0.05) the contraction to vasopressin in ear (148% of control), basilar (150% of control), renal (304% of control), coronary (437% of control) and saphenous (235% of control) arteries. Removal of the endothelium increased significantly (P < 0.05) the contraction to vasopressin in basilar (138% of control), renal (253% of control), coronary (637% of control) and saphenous (662% of control) arteries, but not in ear artery. Mesenteric and pulmonary arteries in the presence of L-NAME or after endothelium removal did not respond to vasopressin, as occurred in control conditions. 4. The specific antagonist for V1 vasopressin receptors d(CH2)5Tyr(Me)AVP (3 x 10(-9)-10(-7) M) was more potent (pA2 = 9.3-10.1) than the antagonist for both V1 and V2 vasopressin receptors desGly-d(CH2)5-D-Tyr(Et)ValAVP (10(-7)-10(-6) M) (pA2 = 7.4-8.4) to block the contraction to vasopressin of ear, basilar, renal and coronary arteries. 5. The specific V2 vasopressin agonist [deamino-Cys1, D-Arg8]-vasopressin (desmopressin) (10(-10)-10(-7) M) did not produce any effect in any effect in any of the arteries studied, with or without endothelium. 6. In arteries precontracted with endothelin-1, vasopressin or desmopressin did not produce relaxation. 7. These results suggest: (a) most arterial beds studied (5 of 7) exhibit contraction to vasopressin with different intensity; (b) the vasoconstriction to this peptide is mediated mainly by stimulation of V1 vasopressin receptors, and (c) endothelial nitric oxide may inhibit the vasoconstriction to this peptide, especially in coronary and renal vasculatures.
  • Article
    Full-text available
    To test the hypothesis whether or not dobutamine or dopamine infusion increases gastric mucosal perfusion, a prospective randomized crossover trial was conducted on 10 septic patients in the intensive care unit of a university hospital. Systemic hemodynamic, oxygen transport, and gastric perfusion assessed by gastric intramucosal pH and laser Doppler flowmetry were measured at baseline and after administration of dobutamine or dopamine (5 micrograms/kg/min). Both increased oxygen transport. In response to dobutamine, gastric mucosal blood flow increased (+32 +/- 14% from baseline; p < 0.05), gastric tonometered PCO2 and gastric arterial PCO2 difference decreased (58 +/- 7 versus 52 +/- 7 mm Hg; p < 0.05; 16.8 +/- 7.0 versus 10.5 +/- 7.2 mm Hg; p < 0.05), and intramucosal pH increased (7.23 +/- 0.05 versus 7.29 +/- 0.06; p < 0.05). In response to dopamine, gastric mucosal blood flow decreased (-28 +/- 8% from baseline; p < 0.05), gastric tonometered PCO2, gastric-arterial PCO2 difference, and calculated intramucosal pH were unchanged (58 +/- 7 versus 61 +/- 9 mm Hg, ns; 16.8 +/- 7.0 versus 18.9 +/- 8.4 mm Hg, ns; 7.24 +/- 0.05 versus 7.21 +/- 0.06, ns). We speculated that despite an oxygen transport increase, dobutamine and dopamine have affected differently gastric mucosal perfusion in septic patients.
  • Article
    Full-text available
    To compare the effects of norepinephrine and dobutamine to epinephrine on hemodynamics, lactate metabolism, and gastric tonometric variables in hyperdynamic dopamine-resistant septic shock. A prospective, intervention, randomized clinical trial. Adult medical/surgical intensive care unit in a university hospital. 30 patients with a cardiac index (CI) > 3.51 x min(-1) x m(-2) and a mean arterial pressure (MAP) < or = 60 mmHg after volume loading and dopamine 20 microg/kg per min and either oliguria or hyperlactatemia. Patients were randomized to receive an infusion of either norepinephrine-dobutamine or epinephrine titrated to obtain an MAP greater than 80 mmHg with a stable or increased CI. Baseline measurements included: hemodynamic and tonometric parameters, arterial and mixed venous gases, and lactate and pyruvate blood levels. These measurements were repeated after 1, 6, 12, and 24 h. All the patients fulfilled the therapeutic goals. No statistical difference was found between epinephrine and norepinephrine-dobutamine for systemic hemodynamic measurements. Considering metabolic and tonometric measurements and compared to baseline values, after 6 h, epinephrine infusion was associated with an increase in lactate levels (from 3.1 +/- 1.5 to 5.9 +/- 1.0 mmol/l;p < 0.01), while lactate levels decreased in the norepinephrine-dobutamine group (from 3.1 +/- 1.5 to 2.7 +/- 1.0 mmol/l). The lactate/pyruvate ratio increased in the epinephrine group (from 15.5 +/- 5.4 to 21 +/- 5.8; p < 0.01) and did not change in the norepinephrine-dobutamine group (13.8 +/- 5 to 14 +/- 5.0). Gastric mucosal pH (pHi) decreased (from 7.29 +/- 0.11 to 7.16 +/- 0.07; p < 0.01) and the partial pressure of carbon dioxide (PCO2) gap (tonometer PCO2-arterial PCO2) increased (from 10 +/- 2.7 to 14 +/- 2.7 mmHg; p < 0.01) in the epinephrine group. In the norepinephrine-dobutamine group pHi (from 7.30 +/- 0.11 to 7.35 +/- 0.07) and the PCO2 gap (from 10 +/- 3.0 to 4 +/- 2.0 mmHg) were normalized within 6 h (p < 0.01). The decrease in pHi and the increase in the lactate/pyruvate ratio in the epinephrine group was transient, since it returned to normal within 24 h. Considering the global hemodynamic effects, epinephrine is as effective as norepinephrine-dobutamine. Nevertheless, gastric mucosal acidosis and global metabolic changes observed in epinephrine-treated patients are consistent with a markedly inadequate, although transient, splanchnic oxygen utilization. The metabolic and splanchnic effects of the combination of norepinephrine and dobutamine in hyperdynamic dopamine-resistant septic shock appeared to be more predictable and more appropriate to the current goals of septic shock therapy than those of epinephrine alone.
  • Article
    Newer techniques for cardiac output (Q) determinations that are minimally invasive remain to be validated in neonatal foals against other accepted techniques such as the lithium technique (LiDCO). This study compares Q determinations using the partial CO2 rebreathing technique (NICO) with LiDCO in anesthetized neonatal foals. Ten foals were instrumented for NICO and LiDCO determinations. For each foal low, intermediate and high levels of cardiac output were achieved in that order using an end-tidal isoflurane (ETI) concentration of 1.3 – 2.1% for the lowest rate; an ETI of 0.85–1.4% and a constant-rate infusion of dobutamine (1–3 ?g/kg/min) for the intermediate rate; and an ETI of 0.83–1% and dobutamine (2–6 ?g/kg/min) for the highest rate. Four foals also received IV intermittent doses (total cumulative dose of 1.1–1.7 mg) of phenylephrine at the highest rate of Q. The measurements were obtained in duplicate or triplicate for each Q technique after achieving a stable hemodynamic plane for at least 15 minutes at each rate of Q. For the lithium technique, all foals received 1.1–1.9 mL (0.16–0.28 mmol) of lithium. A Bland-Altman analysis was used to compare the bias and precision of the two techniques. Eighty seven comparisons were determined between the two techniques. Eight were excluded due to more than 20% variation between the LiDCO determinations or technical errors at the time of determination. The correlation coefficient between the two methods was 0.67 for all Q determinations. Mean LiDCO and NICO values from 79 measurements were 130 ± 40 mL–1 kg minute–1 (range, 68– 237) and 152 ± 31 mL–1 kg minute–1 (89 – 209), respectively. The mean ( mL–1 kg minute–1) of the differences of LiDCO – NICO was = –0.7248 + 0.8602 NICO. The precision (1.96 SD) of the differences between LiDCO and NICO was 58.9 mL–1 kg minute–1 (–80.9–+36.9) with a mean difference of –22 mL–1 kg minute–1 (bias; 95% CI – 15.2 to -28.7). In conclusion, given the small bias compared to the limits of agreement, the NICO technique for determining Q deserves further consideration for adoption into clinical practice in neonatal foals.
  • Article
    To evaluate the effect on intramuscular blood flow (IMBF) and hemodynamic variables of 4 antihypotensive agents given during anesthesia. 8 ponies. Halothane-anesthetized ponies (n = 6) positioned in lateral recumbency received, on separate occasions, infusions of each of the following 4 agents in serially increasing dosages or saline solution: phenylephrine hydrochloride (0.25, 0.5, 1, and 2 microg/kg of body weight), dopamine (2.5, 5, 10, and 20 microg/kg), dobutamine (1, 2.5, 5, and 10 microg/kg), and dopexamine (0.5, 1, 5, and 10 microg/kg). Changes in IMBF (by laser-Doppler flowmetry) in nondependent and dependent triceps brachii muscles and cardiopulmonary variables were measured. Phenylephrine at all dosages failed to improve IMBF or cardiac index (CI), but increased mean arterial pressure (MAP) and systemic vascular resistance (SVR); 2 ponies had forelimb lameness on recovery. Dopamine (10 microg/kg/min) increased CI, MAP, and IMBF in the dependent muscle. A higher dose (20 microg/kg/min) caused cardiac arrhythmias and muscular tremor. Dobutamine increased Cl, MAP, and IMBF of both forelimbs, effects being significant for 2.5 microg/kg/min, with further improvement as the dosage increased. In 2 ponies, 10 microg of dobutamine/kg/min caused cardiac arrhythmias. Dopexamine (1 and 5 microg/kg/min) increased CI, MAP, and IMBF in the nondependent muscle, and 10 microg/kg/min caused muscular tremor, sweating, and arrhythmias. SVR was reduced after infusion of dopamine, dobutamine, or dopexamine. During anesthesia of equids, an increase in Cl and MAP is necessary to improve IMBF in the dependent forelimb. Of the agents investigated, dobutamine proved the most consistent in improving IMBF.
  • Article
    The present study was undertaken to examine whether arginine vasopressin (AVP) relaxes primate coronary artery and to analyse the mechanisms of its action in reference to endothelial nitric oxide and AVP receptor subtype. Isometrical tension responses to AVP and desmopressin were recorded in isolated monkey coronary arteries. AVP (10(-9) to 10(-7) mol/l) induced a concentration-related relaxation; endothelium-denudation abolished the response. Treatment with N(G)-nitro-L-arginine, but not the D-enantiomer, abolished the endothelium-dependent relaxation, which was restored by L-arginine. Treatment with SR49059 and [Pmp1,Tyr(Me)2]-Arg8-vasopressin, selective inhibitors of V1 receptor subtype, attenuated the relaxant response to AVP, whereas the relaxation induced by sodium nitroprusside was not affected by SR49059. Desmopressin, a V2 receptor agonist, up to 10(-8) mol/l did not elicit relaxation. It is concluded that AVP-induced monkey coronary arterial relaxation is mediated via nitric oxide synthesized from L-arginine in association with stimulation of V1 receptor subtypes in the endothelium.
  • Article
    A new automated system of air tonometry (Tonocap; Datex Ohmeda, Helsinki, Finland) allows for frequent (every 15 min) measurement of gastric luminal partial pressure of carbon dioxide. Its use has not been described in cardiac surgical patients. One hundred patients undergoing coronary artery bypass graft or cardiac valve surgery were enrolled in a prospective cohort study. After anesthetic induction and insertion of a TRIP NGS Catheter (Datex Ohmeda), measurements of gastric luminal partial pressure of carbon dioxide were obtained using the Tonocap, and gastric mucosal pH (pHi) was calculated. The main outcome measure was postoperative complication, defined as either in-hospital death or prolonged postoperative hospitalization (> 14 days). Four patients (4%) died, all of multiple-system organ failure, one each on postoperative days 9, 26, 46, and 121. Postoperative complication occurred in 18 patients (18%), all of whom exhibited persistent dysfunction of at least one organ system. Perioperatively, an abnormal pHi (< 7.32) and gastric luminal minus arterial partial pressure of carbon dioxide gap (> 8 mmHg) occurred in 66% and 70% of patients, respectively. Predictors of postoperative complication included postoperative pHi (P = 0.001), gastric luminal partial pressure of carbon dioxide (P = 0.022), and gastric luminal minus arterial partial pressure of carbon dioxide gap (P = 0.013). In contrast, arterial base excess (P > 0.4) and routinely measured hemodynamic variables (e.g., heart rate, blood pressure) were either less predictive compared with Tonocap-derived variables or not predictive. Despite a low mortality rate, patients undergoing cardiac surgery exhibited high incidences of prolonged hospitalization and postoperative morbidity. The Tonocap was easy to use, particularly compared with saline tonometry. Several Tonocap-derived variables were predictive of postoperative complications consistent with previously published data using saline tonometry.
  • Article
    We studied the role of cardiac and arterial baroreceptors in the reflex control of arginine vasopressin (AVP) and renin secretion during graded hypotension in conscious dogs. The dogs were prepared with Silastic cuffs on the thoracic inferior vena cava and catheters in the pericardial space. Each experiment consisted of a control period followed by four periods of inferior vena caval constriction, during which mean arterial pressure (MAP) was reduced in increments of approximately 10 mmHg. The hormonal responses were measured in five dogs under four treatment conditions: 1) intact, 2) acute cardiac denervation (CD) by intrapericardial infusion of procaine, 3) after sinoaortic denervation (SAD), and 4) during combined SAD+CD. The individual slopes relating MAP to plasma AVP and plasma renin activity (PRA) were used to compare the treatment effects using a 2 x 2 factorial analysis. There was a significant (P < 0.01) effect of SAD on the slope relating plasma AVP to MAP but no effect of CD and no SAD x CD interaction. In contrast, the slope relating PRA and MAP was increased (P < 0.05) by SAD but was not affected by CD. These results support the hypothesis that stimulation of AVP secretion in response to graded hypotension is primarily driven by unloading arterial baroreceptors in the dog.
  • Article
    Unlabelled: We sought to evaluate the efficacy and side effect profile of a small dose of ornipressin, a vasopressin agonist specific for the V1 receptor, administered to reverse the hypotension associated with combined general/epidural anesthesia. A total of 60 patients undergoing intestinal surgery were studied. After the induction of anesthesia, 7-8 mL of bupivacaine 0.5% with 2 microg/kg clonidine and 0.05 microg/kg sufentanil after an infusion of 5 mL of bupivacaine 0.06% with 0.5 microg x kg(-1) x h(-1) clonidine and 0.1 microg/h of sufentanil were administered by an epidural catheter placed at T7-8 vertebral interspace. When 20% reduction of baseline arterial blood pressure developed, patients were randomly assigned to receive, in a double-blinded design, dopamine started at 2 microg x kg(-1) x min(-1), norepinephrine started at 0.04 microg x kg(-1) x min(-1), or ornipressin started at 1 IU/h. Fifteen patients presenting without hypotension were used as control subjects. Beside routine monitoring, S-T segment analysis, arterial lactacidemia, and gastric tonometry were performed. Ornipressin restored arterial blood pressure after 8 +/- 2 vs 7 +/- 3 min in the norepinephrine group and 11 +/- 3 min in the dopamine group (P < 0.05). This effect was achieved with 2 IU/h of ornipressin in most of the patients (11 of 15). Ornipressin did not induce any modification of the S-T segment; however, it significantly increased intracellular gastric PCO(2) (P < 0.05), indicating splanchnic vasoconstriction. Implications: In the population studied, small-dose ornipressin was effective to restore arterial blood pressure without causing major ischemic side effects.
  • Article
    We have proposed that the reflex increase in arginine vasopressin (AVP) secretion in response to hypovolemia is due to arterial baroreceptor unloading. If arterial pressure is the key to the mechanism, the slope relating plasma AVP to arterial pressure should be the same in response to hemorrhage, a model of true hypovolemia, and in response to thoracic inferior vena caval constriction (IVCC), a model of central hypovolemia. We tested this hypothesis in conscious, chronically instrumented dogs (n = 8). The mean coefficient of determination (r(2)) values obtained from the individual regressions of log AVP onto systolic pressure (SP) and mean arterial pressure (MAP) in response to hemorrhage were 0.953 +/- 0.009 and 0.845 +/- 0.047, respectively. Paired comparisons indicated a significant difference between the means (P < 0.05), hence, SP was used in subsequent analyses. The mean slopes relating the log of plasma AVP to SP in response to hemorrhage and IVCC were -0.034 +/- 0.003 and -0.032 +/- 0.002, respectively, and the means were not significantly different (P = 0.7). The slopes were not altered when the experiments were repeated during acute blockade of cardiac receptors by intrapericardial procaine. Finally, sinoaortic denervation (n = 4) markedly reduced the slope in both the hemorrhage and IVCC treatments. We conclude that baroreceptors monitoring arterial pressure provide the principal reflex control of AVP secretion in response to hypovolemia.
  • Article
    To measure the effects of increasing mean arterial pressure (MAP) on systemic oxygen metabolism and regional tissue perfusion in septic shock. Prospective study. Medical and surgical intensive care units of a tertiary care teaching hospital. Ten patients with the diagnosis of septic shock who required pressor agents to maintain a MAP > or = 60 mm Hg after fluid resuscitation to a pulmonary artery occlusion pressure (PAOP) > or = 12 mm Hg. Norepinephrine was titrated to MAPs of 65, 75, and 85 mm Hg in 10 patients with septic shock. At each level of MAP, hemodynamic parameters (heart rate, PAOP, cardiac index, left ventricular stroke work index, and systemic vascular resistance index), metabolic parameters (oxygen delivery, oxygen consumption, arterial lactate), and regional perfusion parameters (gastric mucosal Pco2, skin capillary blood flow and red blood cell velocity, urine output) were measured. Increasing the MAP from 65 to 85 mm Hg with norepinephrine resulted in increases in cardiac index from 4.7+/-0.5 L/min/m2 to 5.5+/-0.6 L/min/m2 (p < 0.03). Arterial lactate was 3.1+/-0.9 mEq/L at a MAP of 65 mm Hg and 3.0+/-0.9 mEq/L at 85 mm Hg (NS). The gradient between arterial P(CO2) and gastric intramucosal Pco2 was 13+/-3 mm Hg (1.7+/-0.4 kPa) at a MAP of 65 mm Hg and 16+/-3 at 85 mm Hg (2.1+/-0.4 kPa) (NS). Urine output at 65 mm Hg was 49+/-18 mL/hr and was 43+/-13 mL/hr at 85 mm Hg (NS). As the MAP was raised, there were no significant changes in skin capillary blood flow or red blood cell velocity. Increasing the MAP from 65 mm Hg to 85 mm Hg with norepinephrine does not significantly affect systemic oxygen metabolism, skin microcirculatory blood flow, urine output, or splanchnic perfusion.
  • Article
    The biological effects of arginine vasopressin (AVP) are mediated by three receptor subtypes: the V1a and V1b receptors that activate phospholipases via Gq/11, and the V2 receptor that activates adenylyl cyclase by interacting with Gs. Isolation of the cDNAs encoding the V1a and V1b receptor subtypes explained the tissue variability of V1 antagonist binding, whereas identification of the cDNA and gene encoding the V2 receptor provided the information to identify the mutations responsible for X-linked nephrogenic diabetes insipidus. Mutations that abrogate the production and/or release of AVP from the pituitary have diabetes insipidus as their most dramatic manifestation, indicating that the maintenance of water homeostasis is the most important physiological role of this neuropeptide. Evidence for a significant role of AVP in blood pressure control, although actively sought, has been scant.
  • Article
    In the initial treatment of a critically ill patient, blood pressure, heart rate, urine output, and central venous pressure guide resuscitative efforts. Despite normalization of these variables, global tissue hypoxia may still persist and has been implicated in the development of multiorgan failure and increased mortality. Definitive management includes intensive care unit admission, pulmonary artery catheterization using mixed venous oxygen saturation (SvO2), and hemodynamic optimization. In the absence of or before definitive management, hemodynamic optimization can be performed using central venous oxygen saturation (ScvO2) as a surrogate. The physiology, technology, clinical uses, and rationale for ScvO2 monitoring are reviewed, including issues regarding physiologic equivalence to SvO2. The clinical use of ScvO2 monitoring, evidence-based outcome implications, and limitations of ScvO2 monitoring will also be examined.
  • Article
    To compare sublingual PCO(2) (PslCO(2)) measurements with gastric intramucosal PCO(2) (PimCO(2)) as well as with the traditional indexes of tissue oxygenation in hemodynamically unstable ICU patients. A prospective, validation study. The medical and coronary ICUs of a community teaching hospital. Consecutive patients with severe sepsis, septic shock, or cardiogenic shock requiring pulmonary artery catheterization for hemodynamic management. During the first 24 h of ICU admission, the PslCO(2), PimCO(2), and blood lactate concentrations as well conventional hemodynamic and oxygenation parameters were recorded every 4 to 6 h. The PslCO(2)-PaCO(2) and PimCO(2)-PaCO(2) differences were used as indexes of tissue dysoxia. These variables were correlated with each other as well as with the traditional markers of tissue oxygenation. Seventy-six data sets were obtained on 22 patients. Fifteen patients had severe sepsis/septic shock, and 7 patients did not have sepsis. A patient with ischemic bowel who had a large PimCO(2)-PslCO(2) difference (60.2 mm Hg) was excluded. The initial PslCO(2) and PimCO(2) measurements were 43.5 +/- 10.4 mm Hg and 42.8 +/- 10.9 mm Hg, respectively (correlation coefficient [r] of 0.86; p < 0.001). The mean PslCO(2) and PimCO(2) for the entire data set were 48.0 +/- 13.4 mm Hg and 46.1 +/- 12.3 mm Hg, respectively (r = 0.78; p < 0.001). Ten patients died. The initial PslCO(2)-PaCO(2) difference was 9.2 +/- 5.0 mm Hg in the survivors and 17.8 +/- 11.5 mm Hg in the nonsurvivors (p = 0.04). The initial PimCO(2)-PaCO(2) difference was 8.4 +/- 4.8 mm Hg in the survivors and 16.1 +/- 13.7 mm Hg in the nonsurvivors (p = 0.08, not significant). The initial PslCO(2)-PaCO(2) difference correlated with the initial mixed venous-arterial CO(2) gradient (r = 0.66; p = 0.001), but correlated poorly with the initial blood lactate concentration (r = 0.38), mixed venous PO(2) (r = 0.05), and systemic oxygen delivery (r = - 0.39). In this study, sublingual capnometry yielded measurements that correlated well with those of gastric tonometry. PslCO(2) may serve as a technically simple and noninvasive clinical measurement of tissue dysoxia in critically ill and injured patients.
  • Article
    Unlabelled: We studied whether endogenous endothelin, like endogenous vasopressin, helps to maintain blood pressure during high epidural anesthesia when efferent sympathetic drive is diminished. On different days, six awake dogs underwent each of the following five interventions: blockade of vasopressin V(1a) receptors using [d(CH(2))(5)Tyr(Me(2))]AVP, (40 microg/kg) or endothelin receptors using tezosentan (3 mg/kg followed by 3 mg. kg(-1). h(-1)) with or without epidural anesthesia (1% lidocaine, intraindividual dose did not differ between experiments), and epidural saline (n = 5). The effects of endothelin- or vasopressin-receptor blockade were analyzed (means +/- SEM) and compared by an analysis of variance for repeated measures (paired Student's t-test, alpha-adjusted, P < 0.05). Vasopressin-receptor blockade decreased blood pressure (10 +/- 2 mm Hg) only in the presence of epidural anesthesia, whereas endothelin-receptor blockade reduced blood pressure both in the presence and absence of epidural anesthesia (12 +/- 3 versus 10 +/- 1 mm Hg). During baseline and each intervention, plasma concentrations of vasopressin and big-endothelin were measured and compared by a Wilcoxon's rank sum test; P < 0.05. Vasopressin concentrations increased during epidural anesthesia and after additional endothelin receptor blockade, but big-endothelin concentrations remained unchanged during each intervention. We conclude that vasopressin acts as a reserve system, as it stabilizes blood pressure specifically during epidural anesthesia, whereas the unchanged concentrations of big-endothelin indicate that the endothelin system is not specifically activated to support blood pressure during epidural anesthesia. Implications: We studied in awake dogs whether endogenous endothelin, like endogenous vasopressin, helps to maintain blood pressure during resting conditions and epidural anesthesia. Only vasopressin was specifically activated to support blood pressure during epidural anesthesia, whereas endothelin supported blood pressure to the same extent during epidural anesthesia and during resting conditions.
  • Article
    Full-text available
    To evaluate the effect of an early dobutamine infusion on gastrointestinal perfusion in patients with severe sepsis. Prospective, randomized, controlled, multicenter clinical study. Six medical and/or surgical intensive care units (ICU) of teaching hospitals. Forty-two patients with severe sepsis. Patients were divided into two groups according to gastric-to-arterial CO2 gap (DeltaCO2) [normal DeltaCO2 group ( n=17): DeltaCO2 < or = 8 mmHg; increased DeltaCO2 group ( n=25): DeltaCO2 > 8 mmHg]. Patients within each group were then randomized to receive either dobutamine (5 microg/kg per min) or saline for 72 h. SAPS II was similar in both groups [group 1: 44.0 (33.0-56.5); group 2: 48.5 (40.5-59.0), p=0.27]. At ICU admission, mean arterial pressure was lower in the high DeltaCO2 group [73.0 (67.0-79.5) mmHg, p=0.03] than in the normal DeltaCO2 group [84.0 (73.7-104.0) mmHg] while blood lactate [normal DeltaCO2 group: 1.6 (0.8-2.3); high DeltaCO2 group: 1.6 (1.1-1.9) mmol/l] was similar for the two groups. DeltaCO2 was significantly lower in the normal DeltaCO2 group [5.0 (2.0-6.0) mmHg)] than in the high DeltaCO2 group [11.0 (10.0-19.0) mmHg]. Dobutamine infusion did not significantly change hemodynamics, blood lactate concentration or tonometric parameters in any group within the first 72 h and had no particular beneficial effect in this population. An early infusion of dobutamine at a fixed dose of 5 microg/kg per min during the first 72 h of severe sepsis does not influence gastric DeltaCO2.
  • Article
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    The rationale for an arginine vasopressin (argipressin) infusion was put forward after it was discovered that patients in shock states might have an endogenous arginine vasopressin deficiency. Subsequently, several investigations impressively demonstrated that arginine vasopressin can successfully stabilise haemodynamics even in advanced vasodilatory shock. We report on physiological and pharmacological aspects of arginine vasopressin, and summarise current clinical knowledge on employing a continuous arginine vasopressin infusion in critically ill patients with catecholamine-resistant vasodilatory shock of different aetiologies. In view of presented experimental evidence and current clinical experience, a continuous arginine vasopressin infusion of approximately 2 to approximately 6 IU/h can be considered as a supplemental strategy to vasopressor catecholamines in order to preserve cardiocirculatory homeostasis in patients with advanced vasodilatory shock. Because data on adverse effects are still limited, arginine vasopressin should be reserved for patients in whom adequate haemodynamic stabilisation cannot be achieved with conventional vasopressor therapy or who have obvious adverse effects of catecholamines that result in further significant haemodynamic deterioration. For the same reasons, arginine vasopressin should not be used as a single, alternative vasopressor agent instead of catecholamine vasopressors. Future prospective studies will be necessary to define the exact role of arginine vasopressin in the therapy of vasodilatory shock.
  • Article
    Vasodilatory shock is a potentially lethal complication of severe disease in critically ill patients. Currently, catecholamines are the most widely used vasopressor agents to support blood pressure, but loss of catecholamine pressor effects is a well-known clinical dilemma. Arginine vasopressin (AVP) has recently been shown to be a potent vasopressor agent to stabilize cardiocirculatory function even in patients with catecholamine-resistant vasodilatory shock. Forty-eight patients with catecholamine-resistant vasodilatory shock were prospectively randomized to receive a combined infusion of AVP and norepinephrine (NE) or NE infusion alone. In AVP patients, AVP was infused at a constant rate of 4 U/h. Hemodynamic, acid/base, single-organ, and tonometrically derived gastric variables were reported before the study and 1, 12, 24, and 48 hours after study entry. For statistical analysis, a mixed-effects model was used. AVP patients had significantly lower heart rate, NE requirements, and incidence of new-onset tachyarrhythmias than NE patients. Mean arterial pressure, cardiac index, stroke volume index, and left ventricular stroke work index were significantly higher in AVP patients. NE patients developed significantly more new-onset tachyarrhythmias than AVP patients (54.3% versus 8.3%). Gastrointestinal perfusion as assessed by gastric tonometry was better preserved in AVP-treated patients. Total bilirubin concentrations were significantly higher in AVP patients. The combined infusion of AVP and NE proved to be superior to infusion of NE alone in the treatment of cardiocirculatory failure in catecholamine-resistant vasodilatory shock.
  • Article
    Unlabelled: We compared the effects of vasopressin and norepinephrine on systemic and splanchnic circulation and metabolism in endotoxin shock in pigs. Twenty-one pigs were randomized to endotoxin shock (Escherichia coli endotoxin infusion) (n = 6), endotoxin and vasopressin (VASO; n = 6), endotoxin and norepinephrine (NE; n = 6), and controls (n = 3). Endotoxin infusion was increased to induce hypotension, after which vasopressin or norepinephrine was started to keep systemic mean arterial blood pressure >70 mm Hg. Regional blood flows and arterial and regional lactate concentrations were measured. Tonometers with microdialysis capillaries were inserted into the stomach, jejunum, and colon. Systemic mean arterial blood pressure >70 mm Hg was achieved in the VASO and NE groups. Vasopressin decreased cardiac output, superior mesenteric artery, and portal vein blood flow, whereas hepatic arterial blood flow increased. Arterial lactate concentration increased from 2.0 mM (1.6-2.1 mM) to 4.7 mM (4.7-4.9 mM) (P = 0.007). Systemic and mesenteric oxygen delivery and consumption decreased and oxygen extraction increased in the VASO group. Vasopressin increased mucosal-arterial PCO(2) gradients in all three locations, whereas luminal lactate release occurred only in the jejunum. Animals in the NE group remained stable. Vasopressin reversed hypotension but decreased systemic and gut blood flow. This was associated with hyperlactatemia, signs of visceral dysoxia, and jejunal luminal lactate release. Implications: Although vasopressin induces vasoconstriction in visceral region, its effects on splanchnic circulation and metabolism during septic-endotoxin shock are still poorly characterized. We evaluated the metabolic and hemodynamic effects of vasopressin and norepinephrine within the splanchnic area in porcine endotoxin shock.
  • Article
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    To study the effect of continuous infusion of vasopressin on the splanchnic circulation in patients with severe septic shock. Prospective clinical study. ICU in a teaching hospital. Eleven consecutive patients with documented septic shock who remained hypotensive despite norepinephrine infusion at a rate > or =0.2 microg/kg/min. Insertion of a gastric tonometry catheter, and continuous infusion of vasopressin 0.04 U/min during 4 h. Measurements and main results: Difference between gastric and arterial CO(2) partial pressure (P[g-a]CO(2) gap), mean arterial pressure, and cardiac index were recorded at baseline and after 15 min, 30 min, 60 min, 120 min, and 240 min. The median P(g-a)CO(2) gap increased from 5 mm Hg at baseline to 19 mm Hg after 4 h (p = 0.022). Mean arterial pressure increased from 61 +/- 13 mm Hg at baseline to 68 +/- 9 mm Hg after 4 h (p = 0.055). No significant changes in cardiac index were noted. In norepinephrine-dependent patients in septic shock, continuous infusion of low-dose vasopressin results in a significant increase of the P(g-a)CO(2) gap compatible with GI hypoperfusion.
  • Article
    Successful treatment with inotropes and vasopressors depends on an understanding of the interplay of flow, pressure, and resistance in the cardiovascular system and an appreciation of the pathophysiologic mechanisms leading to inadequate tissue perfusion. Any treatment strategy is necessarily a compromise between the requirements of different vascular beds.Furthermore. the underlying hemodynamic derangements can change rapidly. Therefore. inotropes and vasopressors should be titrated to measures of improved hemodynamic status, and the treatments should be frequently reviewed.
  • Article
    In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for vasopressor and inotropic support in septic shock that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and to improve outcome in severe sepsis. The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. The modified Delphi methodology used for grading recommendations built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations to contrast adult and pediatric management are in the article by Parker et al. on p. S591. An arterial catheter should be placed as soon as possible in patients with septic shock. Vasopressors are indicated to maintain mean arterial pressure of <65 mm Hg, both during and following adequate fluid resuscitation. Norepinephrine or dopamine are the vasopressors of choice in the treatment of septic shock. Norepinephrine may be combined with dobutamine when cardiac output is being measured. Epinephrine, phenylephrine, and vasopressin are not recommended as first-line agents in the treatment of septic shock. Vasopressin may be considered for salvage therapy. Low-dose dopamine is not recommended for the purpose of renal protection. Dobutamine is recommended as the agent of choice to increase cardiac output but should not be used for the purpose of increasing cardiac output above physiologic levels.
  • Article
    Vasopressin is a nonapeptide synthesised in the hypothalamus and released upon stimulations such as hyperosmolality, hypotension and hypovolaemia. In acute shock states serum vasopressin levels increase rapidly and decrease in prolonged septic shock. The administration of vasopressin in healthy subjects has little effect, whereas in vasodilatory shock it increases the mean arterial pressure through V1 receptors and decreases the cardiac output. Vasopressin stimulates the V2 receptors in the kidney leading to reabsorption of water through aquaporin 2. However, in vasodilatory shock the antidiuretic effects are overcome by the effect vasopressin has on the kidneys: improvement of renal blood flow leading to water excretion. Twenty-four studies on the use of vasopressin in patients with vasodilatory shock are reviewed. They show that vasopressin potentiates norepinephrine effects, increases blood pressure significantly in patients with vasodilatory shock and may improve renal function. Side effects ranging from ischaemic skin lesions to possible intestinal ischaemia should not be underestimated. Above a dose of 0.04 U/min it may lead to cardiac arrest. Effects on mortality cannot be interpreted from these studies. Broad clinical use should await controlled trials to clarify its effects on clinical outcomes such as organ failure and mortality.
  • Article
    We investigated intestinal oxygen supply and mucosal tissue PO2 during administration of increasing dosages of continuously infused arginine vasopressin (AVP) in an autoperfused, innervated jejunal segments in anesthetized pigs. Mucosal tissue PO2 was measured by employing two Clark-type surface oxygen electrodes. Oxygen saturation of jejunal microvascular hemoglobin was determined by tissue reflectance spectrophotometry. Microvascular blood flow was assessed by laser-Doppler velocimetry. Systemic hemodynamic variables, mesenteric venous and systemic acid-base and blood gas variables, and lactate measurements were recorded. Measurements were performed at baseline and at 20-min intervals during incremental AVP infusion (n = 8; 0.007, 0.014, 0.029, 0.057, 0.114, and 0.229 IU.kg(-1).h(-1), respectively) or infusion of saline (n=8). AVP infusion led to a significant (P < .05), dose-dependent decrease in cardiac index (from 121 +/- 31 to 77 +/- 27 ml.kg(-1).min(-1) at 0.229 IU.kg(-1).h(-1)) and systemic oxygen delivery (from 14 +/- 3 to 9 +/- 3 ml.kg(-1).min(-1) at 0.229 IU.kg(-1).h(-1)) concomitant with an increase in systemic oxygen extraction ratio (from 31 +/- 4 to 48 +/- 10%). AVP decreased microvascular blood flow (from 133 +/- 47 to 82 +/- 35 perfusion units at 0.114 IU.kg(-1).h(-1)), mucosal tissue PO2 (from 26 +/- 7 to 7 +/- 2 mmHg at 0.229 IU.kg(-1).h(-1)), and microvascular hemoglobin oxygen saturation (from 51 +/- 9 to 26 +/- 12% at 0.229 IU.kg(-1).h(-1)) without a significant increase in mesenteric venous lactate concentration (2.3 +/- 0.8 vs. 3.4 +/- 0.7 mmol/l). We conclude that continuously infused AVP decreases intestinal oxygen supply and mucosal tissue PO2 due to a reduction in microvascular blood flow and due to the special vascular supply in the jejunal mucosa in a dose-dependent manner in pigs.
  • Article
    To measure the effects of increasing mean arterial pressure on oxygen variables and renal function in septic shock. Prospective, open-label, randomized, controlled study. Medical-surgical intensive care unit of a tertiary care teaching hospital. Twenty-eight patients with a diagnosis of septic shock who required fluid resuscitation and pressor agents to increase and maintain mean arterial pressure > or =60 mm Hg. Patients were treated with fluid and norepinephrine to achieve and maintain a mean arterial pressure of 65 mm Hg. Then they were randomized in two groups: In the first group (control group, n = 14), mean arterial pressure was maintained at 65 mm Hg, and in the second group (n = 14), mean arterial pressure was increased to 85 mm Hg by increasing the dose of norepinephrine. Hemodynamic variables (mean arterial pressure, heart rate, mean pulmonary artery pressure, pulmonary artery occlusion pressure, cardiac index, systemic vascular resistance index, pulmonary vascular resistance index, left and right ventricular stroke indexes), metabolic variables (oxygen delivery, oxygen consumption-calorimetric method, arterial lactate), and renal function variables (urine flow, serum creatinine, creatinine clearance) were measured. After introduction of norepinephrine, similar values of hemodynamic, metabolic, and renal function variables were obtained in both groups. No changes were observed in group 1 during the study period. Increasing mean arterial pressure from 65 to 85 mm Hg with norepinephrine in group 2 resulted in a significant increase in cardiac index from 4.8 (3.8-6.0) to 5.8 (4.3-6.9) L.min.m. Arterial lactate and oxygen consumption did not change. No changes were observed in renal function variables: urine flow, 63 (14-127) and 70 (15-121) mL; serum creatinine, 170 (117-333) and 153 (112-310) mumol.L; and creatinine clearance, 50 (12-77) and 67 (13-89) mL.min.1.73 m. Increasing mean arterial pressure from 65 to 85 mm Hg with norepinephrine neither affects metabolic variables nor improves renal function.
  • Article
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    The aims of this study were to compare and contrast the development of the cardiac baroreflex and endocrine responses to acute hypotensive stress in healthy newborn pony foals and lambs during the first two weeks of postnatal life. Under general anaesthesia, seven Welsh pony foals and six Welsh Mountain lambs were catheterised with hind limb artery and vein catheters. Following post-surgical recovery, at 1 week and 2 weeks of age, blood pressures of the animals were raised and lowered acutely by intravenous infusion of phenylephrine and sodium nitroprusside, respectively. During hypotension, blood samples were taken for measurement of plasma hormones associated with activation of the stress axis. Basal arterial blood pressure increased significantly (P<0.05) between week 1 and week 2 in the absence of any significant change in basal heart rate in foals and with a significant reduction in basal heart rate in lambs. In foals, the slope of the heart rate-blood pressure relationship decreased in response to acute hypertension, and it increased in response to acute hypotension, from week 1 to week 2 (all P<0.05). In contrast, in lambs, the slope of the heart rate-blood pressure relationship decreased with both acute hypertension and acute hypotension from week 1 to week 2 (all P<0.05). In foals, there were significant increases in plasma concentrations of noradrenaline, neuropeptide Y (NPY), vasopressin, adrenocorticotrophic hormone (ACTH) and cortisol in response to hypotension (P<0.05). In lambs, there were also significant increases in plasma concentrations of ACTH and cortisol during hypotension. Plasma concentrations of noradrenaline, NPY and vasopressin were not measured during hypotension in lambs. In foals, although the magnitude of the ACTH response to hypotension was smaller at week 2 than week 1, the increment in plasma cortisol was similar in the two age groups. In contrast, in lambs, the profile of both the ACTH and cortisol responses was similar at week 1 and week 2. These data suggest that the increase in basal arterial blood pressure in the foal and the lamb during the first 2 weeks of postnatal life is accompanied by differential maturational changes in the vagal and sympathetic components of the cardiac baroreflex between the two species. These developmental cardiac baroreflex changes occur together with increased adrenocortical responsiveness to acute hypotensive stress, which appears comparatively more mature in lambs than in foals.
  • Article
    The objectives of this study were to assess, in anesthetized neonatal foals, the accuracy of 2 automated indirect oscillometric monitors for measurement of mean arterial pressure (MAP), to determine the optimal site of cuff placement for MAP monitoring, and to determine the relationship between arterial blood pressure and cardiac output. Ten neonatal foals were anesthetized and instrumented with a catheter in the metatarsal artery for direct MAP monitoring and measurement of cardiac output by lithium dilution. Concurrent MAP measurements were obtained with Cardell and Dinamap oscillometric monitors with cuffs placed at 3 different sites (coccygeal, metatarsal, and median arteries). Blood pressure was manipulated by varying the depth of anesthesia and by administration of dobutamine or phenylephrine. A statistically significant (P = .025) interaction was found between the type of monitor and cuff placement site. With the Cardell monitor, placement of the cuff over the coccygeal artery resulted in a significantly lower bias than placement over the median or dorsal metatarsal artery (P < .0001 and P = .0149, respectively). No significant difference in bias was found with cuff placement site when using the Dinamap monitor. The correlation coefficient (r) between MAP and cardiac output was 0.47. Indirect oscillometry with a cuff placed over the coccygeal artery or dorsal metatarsal artery is an acceptable method for measuring MAP in foals. Blood pressure does not correlate well with cardiac output in anesthetized foals.
  • Article
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    In this study we aimed to clarify the role of endothelin in arterial pressure regulation during anaesthesia with increasing concentrations of sevoflurane (1-3 MAC) and compare it with those of vasopressin and angiotensin. After an awake control period, on different days, six dogs underwent each of the following four interventions: sevoflurane anaesthesia alone (1-3 MAC), sevoflurane after block of either endothelin receptors using tezosentan (3 mg kg(-1) followed by 3 mg kg(-1) h(-1)), vasopressin V(1a) receptors using [d(CH(2))(5)Tyr(Me(2))]AVP (40 micro g kg(--1)) or angiotensin receptors using losartan (6 mg kg(-1) h(-1)). Plasma concentrations of endothelin, big endothelin, vasopressin and renin were measured. Effects of sevoflurane in the presence and absence of the respective receptor block were analysed and compared using analysis of variance for repeated measures (ANOVA followed by Fisher's PLSD (protected least significant difference) (P<0.05)). Mean arterial pressure decreased in a dose-dependent manner with sevoflurane during all interventions. At 1 MAC, this decrease was greatest during angiotensin receptor block (mean (SEM), -41 (3) mm Hg), intermediate during vasopressin and endothelin receptor block (-31 (4) and -30 (2) mm Hg respectively), and least during sevoflurane alone (-24 (3) mm Hg). The course of systemic vascular resistance mirrored the course of arterial pressure, while cardiac output did not differ between groups. Plasma concentrations of endothelin, big endothelin and renin did not change during any intervention, whereas vasopressin concentration increased from approximately 0.5 to 40 ng litre(-1) at 3 MAC as arterial pressure decreased in all groups. At 1 MAC, angiotensin attenuated the decrease in arterial pressure during sevoflurane anaesthesia more than endothelin and vasopressin. However, at higher MAC only vasopressin was specifically activated to partly compensate for the arterial pressure decrease.
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