Improved anesthesia for deep surface-induced hypothermia: the halothane-diethyl ether azeotrope.

The halothane-diethyl ether azeotrope was evaluated in dogs as the anesthetic agent for deep surface hypothermia with total circulatory arrest for open-heart operation. All 10 animals given azeotrope in 100% oxygen (O2) experienced atrial arrhythmias during cooling, and 1 had ventricular fibrillation prior to the completion of cooling at 18 degrees to 20 degrees C. After only 30 minutes' arrest, 8 of the 10 dogs had postoperative motor disturbances. Administering the azeotrope in 95% O2 and 5% carbon dioxide (CO2) yielded markedly improved results characterized by a rapid, smooth cooling course, easy resuscitation following circulatory arrest, and rapid rewarming, and 3 out of 10 dogs experienced mild motor disturbance after 60 minutes of circulatory arrest. This method, when compared with our standard method of ether in 100% O2, resulted in reduced blood lactates and a striking improvement in clinical status on the first postoperative morning. In limited clinical trials, infants undergoing repair of congenital cardiac defects have done well and responded as expected based on the laboratory experience. Since the results with the azeotrope in 95% O2 and 5% CO2 were at least as good as, and in several instances better than, those with the standard method employing either, the nonexplosive characteristic of the azeotrope warrants continued evaluation of this agent.

Circulatory dynamics during surface-induced hypothermia under halothane-ether azeotrope anesthesia.

Circulatory dynamics during surface- induced deep hypothermia using the halothane-diethyl ether azeotrope in 100% oxygen (O2) without circulatory arrest and 95% O2 and 5% carbon dioxide (CO2) with and without 60 minutes of arrest were evaluated in 15 adult mongrel dogs. Mean arterial pressure was lower in animals given 5% CO2 than in animals given 100% O2 during cooling. Cardiac output in the 5% CO2 groups increased until 30 degrees C cooling and then gradually decreased to 29% of control at 20 degrees C. Cardiac output in the 100% O2 group progressively decreased to 16% of control at 20 degrees C cooling and was 51 to 77% of the output in the 5% CO2 animals at comparable temperatures throughout the hypothermia procedure. The differences in cardiac output were attributed primarily to changes in stroke volume since heart rates were not significantly different. These changes were probably secondary to differences in systemic vascular resistance, which had increased sixfold in the animals given 100% O2 and had only doubled in the 5% CO2 groups at 20 degrees C during cooling. Hemodynamic variables in animals given 5% CO2 did not reveal significant differences in arrested versus nonarrested animals during early rewarming. However, with further warming, cardiac output, stroke volume, left ventricular stroke work, and mean pulmonary arterial and pulmonary artery wedge pressures were lower, and systemic and pulmonary vascular resistances were higher in the arrest group. We conclude that the improved results with halothane-diethyl ether azeotrope in 95% O2 and 5% CO2 during surface hypothermia are due to a greater cardiac output and reduced peripheral vascular resistance.

Electrocardiographic changes during surface-induced deep hypothermia. The influence of ether, halothane, carbon dioxide, and perfusion rewarming.

The influence of halothane, ether, carbon dioxide, and perfusion rewarming on the electrocardiogram was studied in 37 dogs subjected to surface-induced deep hypothermia. Significant anesthetic-related differences in P-R, QRS, Q-T and R-R intervals during cooling were not apparent; however, reduced arterial pressure, ventricular fibrillation, and a greater tendency for bradycardia requiring supportive measures were noted at low temperatures with halothane anesthesia. The use of 95% O2/5% CO2 significantly reduced the QTc at low temperatures; Other phenomena, including the occurrence and significance of J waves, are discussed. The relationship of the electrocardiogram to clinical and pathological results was evaluated and indicates that (1) properly managed resuscitation (manual massage and defibrillation) is not a serious hazard, (2) ether in 100% oxygen is the agent of choice for surface-induced deep hypothermia with prolonged circulatory arrest, and (3) halothane may be used in a procedure combining surface cooling and perfusion rewarming if given in a mixture of oxygen and carbon dioxide.

The use of Forane anesthesia for surface-induced deep hypothermia.

The effects of Forane anesthesia for deep surface hypothermia with 30 minutes of total circulatory occlusion were evaluated. With 100% O2 6 of 7 dogs developed motor disorders postoperatively, while 3 of 5 with 98% O2/2% CO2 and none with 95% O2/5% CO2 developed motor disorders. Cooling was uneventful except for 1 episode of ventricular fibrillation in the 5% CO2 group at 23 degrees C. Resuscitation was easy, but the early rewarming period was characterized by repeated episodes of ventricular fibrillation and delayed recovery of cardiac function, especially in the 100% O2 group. Blood lactate levels remained low during cooling and gradually increased during rewarming in all groups, with the highest levels in the 100% O2 group and the lowest in the 5% CO2 group. It is concluded that Forane can be used for surface hypothermia with 30 minutes' circulatory occlusion when administered in 95% O2/5% CO2. A Comparison of these results with previously reported series indicates that Forane is inferior to ether but may be superior to halothane for surface hypothermia.

Biogenic monoamine turnover in discrete rat brain regions is correlated with conditioned emotional response and its conditioning history.

The content and turnover of dopamine, norepinephrine and 5-hydroxytryptamine (serotonin), and the content of their respective major metabolites were evaluated in 19 discrete brain areas of rats exposed to conditioned emotional response (CER), and in control groups which received either equivalent yoked shock (shock only) or compound stimulus presentation (tone only). On test day, CER animals suppressed responding and exhibited forms of emotional behavior after presentation of the conditioned stimulus (CS); while shock only and tone only control groups, and CER animals which received an acute dose of diazepam prior to testing, did not suppress. Few changes were observed in content of the biogenic amines or their metabolites, suggesting that the behavioral manipulations were acting within normal physiological limits. On the other hand, numerous changes were observed in the utilization of the 3 biogenic monoamines, which were correlated with the conditioning-anxiety (comparisons of CER vs shock only) and the shock history (comparison of shock only vs tone only). These observations are consistent with putative neural pathways in the frontal cortex, septum, nucleus accumbens, amygdala, striatum, hippocampus and brain stem (which utilize specific monoamines), and with discrete brain areas which have been implicated in classical conditioning and CER-related phenomena. These observations suggest roles for biogenic monoamines in mediating or responding to the classical conditioning and emotional components of the paradigm.

Amino acid neurotransmitter utilization in discrete rat brain regions is correlated with conditioned emotional response.

The content and utilization of amino acid neurotransmitters were evaluated in discrete brain areas of rats exposed to a conditioned emotional response (CER) procedure and in control groups which received either equivalent yoked shock history (shock only) or compound stimulus presentation (tone only). On test day, CER animals suppressed responding and exhibited anxious behavior after presentation of the CS, while shock only and tone only control groups, or CER animals which received an acute dose of diazepam prior to testing, did not suppress. Few changes were observed in the content of amino acids, suggesting that the behavioral manipulations were acting within normal physiological limits. On the other hand, numerous changes were observed in the utilization (turnover, metabolism) of the amino acid neurotransmitters. The effects of a history of shock presentation (shock only versus tone only) were persistent long after the conditioning sessions were terminated, and resulted in decreased turnover of the amino acids in many areas. CER conditioning-emotion (CER versus shock only) produced an increase in the turnover of aspartate and glutamate in many structures, while changes in GABA turnover were generally limited to decreases in limbic areas. If CER represents an animal model of anxiety, these observations may suggest roles for neurons which utilize amino acids in mediating or responding to emotional components of the paradigm.

The importance of appropriate concentrations of inspired carbon dioxide on induced hypothermia under halothane-ether azeotrope anesthesia.

Thirty adult mongrel dogs were divided into 3 equal groups and studied to define the optimal PCO2 level with azeotrope (halothane-diethyl ether) anesthesia under surface hypothermia (Groups I, II and III = F1CO2 0%, 5% and 10%, respectively). All animals were cooled to 18-20 degrees C and were subjected to 30 (Group I) or 60 minutes (Groups II and III) of total circulatory arrest. Group I animals had frequent arrhythmic episodes during cooling and postoperative motor disturbances occurred in 80% despite only 30 minutes of circulatory arrest. By contrast Group II animals were less arrhythmic during cooling; were easily resuscitated following 60 minutes of arrest and only 30% developed moderate reversible motor disturbances postoperatively. Hemodynamics were similar between Groups II and III during cooling but resuscitation using an F1CO2 of 10% (Group III) was extremely difficult and required massive cardiotonic support throughout rewarming. Furthermore, two dogs in Group III died within the first two postoperative days. However, none of the 8 survivors displayed neurological abnormalities. On balance, a ventilatory regimen utilizing 5% CO2 during surface-induced hypothermia under azeotrope anesthesia resulted in optimum intraoperative management and a satisfactory postoperative course and although some CNS disturbance (high-stepping gait) was noted, all animals recovered completely.

Prolongation of the safe interval of hypothermic circulatory arrest: 90 minutes.

Twenty-nine adult mongrel dogs were subjected to profound hypothermia and 90 minutes of total circulatory arrest. Pure surface (Group I) hypothermia and combined surface/perfusion techniques with bubble (Group II) and membrane (Group III) oxygenator systems were employed. Circulation was arrested at average esophageal temperatures of 18.4 degrees, 11.9 degrees and 8.5 degrees C in Groups I, II and III, respectively. Three animals in Group I failed to resuscitate. All survivors in the pure surface series developed postoperative gait (hypermetria) disturbances. One intraoperative death occurred in Group II and four of eight dogs arrested at esophageal temperatures above 10 degrees C but less than 15 degrees C developed motor disturbances during a three week neurologic evaluation period. Animals arrested below 10 degrees C (esophageal) did not display postoperative neurological abnormalities. Three dogs in Group III died from a hemorrhagic diathesis of uncertain etiology. None of the survivors (5) that were cooled and arrested below esophageal temperatures of 10 degrees C developed motor or sensory disturbances. We conclude that in the canine model the central nervous system can be protected for 90 minutes of total circulatory arrest at esophageal temperatures less than 10 degrees C.

Lipoinjection as a treatment of pacemaker pocket neuralgia.

Chronic severe pacemaker pocket neuralgia secondary to inadequate subcutaneous tissue between the pacemaker and overlying skin typically is treated by surgical pocket revision or relocation of the system. A case of this complication successfully treated by lipoinjection is reported. Additional experience is needed to confirm the usefulness of the technique as a means of providing symptomatic relief without the risks associated with more invasive procedures.

Whole body protection during three hours of total circulatory arrest: an experimental study.

Survival following 3 hr of total circulatory arrest under profound hypothermic conditions was explored in 19 adult mongrel dogs. Thermoregulatory management included combined surface/perfusion hypothermia and azeotrope anesthesia in 95% O2/5% CO2. All animals were resuscitated and survived for at least 12 hr. During the last seven trials (Group II) the following principles were applied: uniform whole-body cooling where differences between rectal, esophageal, and pharyngeal temperatures averaged less than 1 degree C, induction of circulatory arrest at approximately 3 degrees C, constant lung inflation (10-12 cm H2O between 20 degrees C cooling and 20 degrees C rewarming, including the 3-hr arrest period) and ventilation assistance with positive end-expiratory pressure (4 cm H2O) after 20 degrees C rewarming, intraoperative maintenance of colloid osmotic pressure (COP) above 11 mm Hg, replacement of the cooling perfusate with a colloid-rich rewarming prime (COP = 15 mm Hg) and restoration of hemostasis with fresh whole blood transfusions. The application of these principles resulted in the long-term survival of five animals with four survivors displaying no clinically detectable neurological abnormalities. However, two animals developed optic impairment and one animal died from intusseption on the fourth postoperative day. Despite the improved results, it should also be noted that during pilot (Group I) studies (from which the aforementioned principles were derived) fatalities from complications attributed to systemic edema, central nervous system, or pulmonary or coagulation dysfunctions occurred in 9 out of 12 trials. We conclude that whole body protection following 3 hr of total circulatory arrest at a uniform temperature less than 5 degrees C can be successfully accomplished.

Neurotransmitter turnover in rat striatum is correlated with morphine self-administration.

Drugs of abuse probably exert their reinforcing effects through 'reward' pathways in the central nervous system (CNS). Neuronal systems mediating opiate reinforcement have been investigated using pharmacological and electrolytic lesion procedures. Drugs that interfere with catecholaminergic and cholinergic neuronal activity decrease intravenous (i.v.) morphine self-administration in monkeys and rats. Electrolytic lesion procedures in rats have demonstrated that the medial forebrain bundle and caudate nucleus are important in maintaining i.v. morphine self-administration. We have now carried out a direct investigation of striatal (caudate nucleus, putamen and globus pallidus) neuronal systems. We show here that striatal catecholaminergic systems are important in mediating opiate reinforcement, and present direct evidence for the involvement of neurotransmitter systems in morphine reward.

Effects of circulatory arrest and rewarming on regional blood flow during surface-induced hypothermia.

Regional blood flow and distribution of cardiac output (CO) were evaluated by the radioactive microsphere technique in rhesus monkeys during surface rewarming following the induction of deep hypothermia (20 degrees C.) under deep ether anesthesia. A comparison of animals subjected to 30 minutes of circulatory arrest and those not arrested revealed cerebral, coronary, and renal vascular resistance and flow patterns consistent with a hyperemic response to circulatory arrest at 20 degrees C. Throughout rewarming cerebral and coronary absolute flows tended to be at or above the flows noted at comparable cooling temperatures in a previous study. Renal flow fraction (% Qt) were well preserved during rewarming to 30 degrees C., but a decrease was observed thereafter. Carcass (muscle, skin, bone) %Qt was also reduced following rewarming, especially in arrested animals. CO appeared to be similar to those noted at comparable cooling temperatures until 30 degrees C. during rewarming; thereafter, CO did not fully recover to awake control levels. These data suggest that regional flow is redistributed from the carcass and renal circulations to cerebral and coronary circulations in response to hemodynamic alterations during surface rewarming. It was concluded that autoregulative responses to both circulatory arrest and hemodynamic factors are elicited during surface rewarming from deep hypothermia to 20 degrees C. with the method described.

Effects of ether anesthesia and surface-induced hypothermia on regional blood flow.

Regional blood flow and distribution of cardiac output (CO) were evaluated by the radioactive microsphere technique in seven rhesus monkeys prior to anesthesia, following the induction of deep ether anesthesia and throughout the cooling course during surface-induced hypothermia to temperatures of 20 degrees C. As given, deep ether anesthesia alone significantly decreased CO 10% to 15% and output fraction (Qt) was decreased to the carcass, increased to the splanchnic circulation (although not statistically significant), and unchanged to other organs, while total vascular (TVR) and organ resistances were reduced. With the addition of cooling, CO progressively decreased. Individual organ Qt's, however, did not change from anesthetized normothermic values; thus organ flows decreased parallel to the reduction of CO as cooling progressed. TVR and organ vascular resistances increased to levels in excess of 150% of anesthetized precooling values, apparently as the result of viscosity rather than vascular changes.