C.J. Lawrence

Effects of a single pre‐operative dexmedetomidine dose on isoflurane requirements and peri‐operative haemodynamic stability

In a double‐blind, placebo‐controlled study we investigated the effect of a single pre‐induction intravenous dose of dexmedetomidine 2 μg.kg−1 on anaesthetic requirements and peri‐operative haemodynamic stability in 50 patients undergoing minor orthopaedic and general surgery. Patients were anaesthetised with nitrous oxide/oxygen/fentanyl, supplemented if necessary with isoflurane. The mean (SD) intra‐operative isoflurane concentration was lower in the dexmedetomidine‐treated patients than controls (0.01 (0.03)% compared to 0.1 (0.1)%; p = 0.001) although six of the 25 treated patients required isoflurane at some stage. The haemodynamic response to tracheal intubation and extubation was reduced in the dexmedetomidine group as was intra‐operative heart rate variability; postoperative analgesic and anti‐emetic requirements and peri‐operative serum catecholamine concentrations were lower in the dexmedetomidine group. Hypotension and bradycardia occurred more frequently after dexmedetomidine.

The effect of dexmedetomidine on nutrient organ blood flow.

The alpha2-adrenergic agonist dexmedetomidine decreases not only heart rate, myocardial contractility, and oxygen demand, but also cardiac output (Q). To investigate whether this reduction in Q could critically impair perfusion of individual organs, we studied the effect of dexmedetomidine on nutrient blood flow to the heart, brain, kidney, spleen, skin, intestine, liver, and arteriovenous anastomoses using the radioactive microsphere technique. Studies were conducted in 14 dogs with an open chest and anesthetized with either chloralose/urethane (CU) or fentanyl/halothane (FH), to create different baseline conditions. Hemodynamic variables, organ blood flow, arterial and mixed venous oxygen, and lactate content were measured before and after administration of 0.1, 1, and 10 micro g/kg dexmedetomidine intravenously (IV). After 10 micro g/kg dexmedetomidine Q decreased in both groups by 50%. The decrease in blood flow varied greatly between the organs. While flow through arteriovenous anastomoses and skin decreased by 70% to 90%, renal blood flow decreased by 30%, cerebral blood flow only when baseline blood flow was high (FH dogs), and left ventricular blood flow only in the CU group, where the largest decrease in hemodynamic variables occurred. Oxygen consumption decreased only in CU dogs, but so did arterial lactate levels. These data indicate that dexmedetomidine causes considerable redistribution of Q, predominantly reducing blood flow to less vital organs and shunt flow. (Anesth Analg 1996;83:1160-5)

The Effect of Dexmedetomidine on the Balance of Myocardial Energy Requirement and Oxygen Supply and Demand

The effect of the alpha2-adrenergic agonist dexmedetomidine on the balance between myocardial energy requirement and oxygen supply and demand was investigated in 16 open-chest dogs anesthetized with either chloralose/urethane (CU) or fentanyl/halothane (FH). Myocardial energy requirement (estimated from the pressure work index), blood flow and its transmural distribution (radioactive microspheres), as well as myocardial oxygen and lactate extraction, were measured before and after administration of dexmedetomidine in doses ranging from 0.1 to 10 micro gram/kg intravenously. Under CU anesthesia, dexmedetomidine decreased heart rate, arterial blood pressure, and cardiac output. During FH anesthesia, dexmedetomidine reduced heart rate and cardiac output whereas arterial blood pressure increased. Dexmedetomidine decreased myocardial energy requirement only during CU anesthesia; myocardial oxygen supply and demand decreased in parallel. At the (large) dose of 10 micro gram/kg, myocardial oxygen extraction increased during both types of anesthesia. Dexmedetomidine >or=to 1 micro gram/kg increased endocardial/epicardial blood flow ratio during FH anesthesia. These data indicate that dexmedetomidine >or=to 1 micro gram/kg reduces myocardial energy requirements, especially when baseline heart rate and blood pressure are increased. Dexmedetomidine preserves endocardial perfusion and reduces oxygen demand in parallel with oxygen supply and energy requirements. (Anesth Analg 1996;82:544-50)

Hemodynamic and coronary vascular effects of dexmedetomidine in the anesthetized goat.

Background: In phase III trials, the hemodynamic stabilising effect of the α2‐adrenergic agonist dexmedetomidine (DEX) is being investigated in patients with coronary artery disease. Coronary vascular effects of α2‐agonists have been studied in dogs and pigs, but both species have a different hemodynamic response to DEX than man. The aim of this study was to investigate the hemodynamic and coronary vascular effects in goats.

Comparative study of isradipine and sodium nitroprusside in the control of hypertension in patients following coronary artery-bypass surgery.

Essential hypertension is a common occurrence after coronary artery bypass–graft surgery (CABG) and may lead to postoperative complications. In an open randomized study, either isradipine or sodium nitroprusside was given by infusion to 27 postoperative CABG patients who had a mean arterial pressure (MAP) greater than 100 raraHg. Both agents were able to achieve reductions in MAP to 80 – 90 mmHg quickly and safely, although the effects of isradipine at the dosage used were apparent sooner and gave smoother control than with sodium nitroprusside. There were two non–responders with the latter agent. Systemic vascular resistance fell and cardiac output increased in patients in both treatment groups. Also, an increase in heart rate was observed with both agents, although this increase was smaller with isradipine. In conclusion, isradipine appears to be a useful agent in the treatment of hypertension following CABG surgery and may have some advantages over sodium nitroprusside.

Alleviation of the peripheral hemodynamic effects of dexmedetomidine by the calcium channel blocker isradipine.

Background: Alpha2‐adrenergic agonists have peripheral vaso‐constrictive effects and central sympatholytic and sedative effects. Whereas the latter are the basis of their use in anesthesia, the former could limit their clinical application.