Anesthetic implications for surgical patients with endocrine tumors.

The preoperative evaluation and safe anesthetic treatment of patients with endocrine gland tumors mandate an understanding of the physiologic dysfunctions attributable to these tumors. Some patients will exhibit various signs and symptoms characteristic of the MEN syndromes. In the patient with acromegaly, a fiberoptic-guided intubation of the trachea to secure the airway before induction of general anesthesia must be anticipated. Anesthetic treatment of the patient with hyperadrenocorticism requires knowledge of the physiologic effect of excess cortisol. In the patient with severe hyperparathyroidism, we attempt to correct the markedly elevated plasma calcium levels and maintain adequate hydration and urine output perioperatively. Following thyroidectomy for MCT, 2 potential problems of concern are upper airway obstruction and aspiration resulting from injury (unilateral or bilateral) to the recurrent laryngeal nerve and the superior laryngeal nerve, respectively. The major focus during excision of an insulinoma is prevention of wide swings in blood glucose concentrations. In the gastrinoma patient, the anesthesiologist not only must correct any intravascular fluid volume deficit or electrolyte imbalance but must also consider the patient to have a full stomach at the time of anesthetic induction. Correction of hypokalemia and control of hypertension may be required in the preoperative preparation of the patient with an adrenal cortex tumor. Preoperative alpha-adrenergic blockade must be initiated in the patient with a pheochromocytoma to prevent dangerous elevations in blood pressure during anesthesia and surgery for the tumor's removal. Vasodilators with rapid onset and short duration are used to treat intraoperative hypertension. After ligation of the tumor's blood supply, falls in blood pressure may require treatment with fluids and vasopressors. Carcinoid syndrome patients should be treated with somatostatin to prevent stimuli such as anxiety, abdominal scrubbing, or tumor manipulation from precipitating severe hypotension, hypertension, bronchospasm, or tachycardia. In both pheochromocytoma and carcinoid patients, a smooth anesthetic induction and tracheal intubation plus avoidance of drugs that release histamine or activate the sympathetic nervous system may also prevent intraoperative crises.

A new method to evaluate cardiovascular response in anesthetized rats. Hypertension after variable intensity, brief electrical stimuli.

To establish and standardize a nociceptive response in anesthetized rats, the hypertensive responses to defined electrical and mechanical stimuli were studied. Rats (n = 7) were given etomidate, 3.8 mg/kg/hr intravenously (i.v.) 2 hr following carotid artery and jugular vein cannulation. At 15 min after beginning the infusion, four types of noxious stimuli were administered sequentially at 1-min intervals (14 stimuli total): Type 1: Square electrical waves, 125 cps, 1.6 msec, 2-sec train duration, varying current from 0.4 to 12 mA (11 stimuli); Type 2: A single 10-mA electrical stimulus, 5-sec train duration; Type 3: Tail clamping; and, Type 4: Skin incision. After each stimulus, maximum change in systolic blood pressure (delta SBP) was measured. delta SBP after the most intense stimuli was as follows: Type 1 (12 mA, 2 sec), 32.1 +/- 2.14 mmHg; Type 2 (10 mA 5 sec), 42.9 +/- 2.4 mmHg; Type 3 (tail-clamping), 34.3 +/- 3.3 mmHg; Type 4 (skin incision), 14.2 +/- 2.8 mmHg. For the multiple Type-2 stimuli, a relationship between current and delta SBP was present. The authors believe that characterized graded electrical stimulation will allow a more quantitative evaluation of the hypertensive response to noxious stimuli in etomidate anesthetized rats, as compared to observing a single response to a single stimulus. The characterization of the electrical stimulation by amplitude, frequency, and wave form makes research work on nociception under anesthesia easily reproducible.

A new model to evaluate the hypertensive response to noxious stimuli in the anesthetized, spontaneously hypertensive rat.

We have developed a method to evaluate the hypertensive response after noxious stimuli in anesthetized rats. Anesthetic level, stimuli, and responses were standardized by using an etomidate infusion, a series of stimuli of increasing intensity applied to the tail, and measuring maximal changes in systolic blood pressure (delta SBP) after each stimulus. Normotensive Sprague Dawley rats (SD) (n = 7) were studied using an etomidate infusion of 4.2 mg.kg-1 x h-1. This method was then applied to spontaneously hypertensive rats (SHR) anesthetized with three rats of etomidate infusion: Group 1 (n = 8), 7.0 mg.kg-1 x h-1; Group 2 (n = 8), 5.6 mg.kg-1 x h-1; and Group 3 (n = 11), 4.2 mg.kg-1 x h-1. Under anesthesia, three types of noxious stimuli were applied to the tail at 1-min intervals (13 total): (a) Type 1:11 2-s electrical stimuli of increasing intensity (0.4-12 mA, to produce threshold to maximal responses); (b) Type 2: one intense, prolonged electrical stimulus (10 mA, 5 s); and (c) Type 3: tail-clamping. After each stimulus, delta SBP was measured. In the SHR, comparing single delta SBP responses to single noxious stimuli after each of the three most intense stimuli showed no statistically significant differences among the three anesthetic groups. In contrast, comparison of dose-response curves of multiple delta SBP responses to multiple Type 1 (2-s) stimuli demonstrated a significant difference among the three anesthetic groups of SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemotherapy resistant sarcoma treated with whole body hyperthermia (WBH) combined with 1-3-bis(2-chloroethyl)-1-nitrosourea (BCNU).

Seventeen patients with chemotherapy-resistant metastatic sarcoma were treated with whole body hyperthermia (WBH) combined simultaneously with 1-3-Bis(2-chloroethyl)-1-nitrosourea (BCNU). All of the patients had chemotherapy resistant metastases to major organ sites. Patients were heated to 41.8-42.0 degrees C for 2 h using an insulated blanket heating technique. Two patients (12%) experienced partial responses (PR). In addition, four objective tumour responses (OR) lasting more than 4 months were documented. One patient with previously rapidly growing chondrosarcoma pulmonary metastases experienced stable disease (SD) for 38 months from the onset of treatment. Median survival of seven patients with responding tumours (PR, OR and SD) compared with 10 patients with progressive disease was 15 versus 2 months, respectively. Cumulative thrombocytopenia was a therapy-limiting toxicity of the combined treatment, and occurred in six of seven patients. Acute toxicities attributable to WBH alone included transient thrombocytopenia in all patients, non-cardiogenic pulmonary oedema in two patients, and mild hypotension in five patients. Acute granulocytosis was observed in all patients. No treatment related deaths occurred. These data suggest that WBH combined with chemotherapy is associated with disease response in patients with chemotherapy-resistant, widely disseminated sarcoma metastases.

The effects of oral transmucosal fentanyl citrate premedication on preoperative behavioral responses and gastric volume and acidity in children.

The authors compared the safety, efficacy, and effects on gastric volume and pH of oral transmucosal fentanyl citrate (OTFC) premedication and of placebo lollipop and no premedication in 55 children undergoing elective operations. The patients were randomly assigned to receive no premedication (group A, N = 18); OTFC containing 15-20 micrograms/kg of fentanyl citrate (group B, N = 18); or a placebo lollipop (group C, N = 19). Activity (sedation) and anxiety scores, vital signs (including systolic and diastolic arterial blood pressures, heart and respiratory rates), and pulse oximetry determined oxygen saturation were measured before and at 10-min intervals after premedication until the patients were taken to the operating room. Gastric contents were aspirated via an orogastric tube and analyzed for volume and pH after induction of anesthesia. Quality of induction and recovery were evaluated using scoring schedules; recovery times were measured and side effects recorded. OTFC was readily accepted and provided levels of sedation and anxiolysis significantly greater after 10 min than after no premedication or the placebo lollipop. Arterial blood pressures, heart rate, and oxygen saturations were not different among the three groups. In patients given OTFC, respiratory rates were significantly lower after 10 min than they were in patients having no premedication.(ABSTRACT TRUNCATED AT 250 WORDS)

Functional and metabolic effects of bupivacaine and lidocaine in the perfused working rat heart.

The effects of bupivacaine (2.5, 5, 10, and 12.5 mg/L) and lidocaine (12.5, 25, 40, and 50 mg/L), on spontaneous heart rate, mean pressure development, cardiac output, and coronary flow were compared after 15 minutes' exposure in the isolated perfused working rat heart preparation. In addition, myocardial oxygen consumption, glucose utilization, lactate production, tissue content of glycogen, adenine nucleotides, and creatine phosphate content were measured. The relative potency of bupivacaine to lidocaine, calculated from slopes of regression equations, as indicated by the four mechanical variables and oxygen consumption, was 4.59. When the bupivacaine concentration was "normalized" using this value, bupivacaine and lidocaine showed indistinguishable effects on glucose utilization, lactate production, and tissue glycogen. Neither of the local anesthetics had any influence on energy charge or creatine phosphate content.

Effect of halothane on glucose utilization in the perfused working rat heart.

To define the mechanism of the cardiodepressant action of halothane, we used the perfused working rat heart to study the effects of the anesthetic on glucose utilization and left ventricular function, both in the absence and presence of insulin. Rates of glucose utilization were measured by the appearance of 3HOH in the coronary effluent derived from 2-3H-glucose added to the media. Lactate production was determined by enzymatic methods. Tissue glycogen was measured by enzymatic methods to calculate total glucose available for energy production by the heart. Halothane, up to 2.4% concentration, had a dose dependent depressant effect on oxygen consumption, mechanical performance, and utilization of media glucose. Exogenous insulin did not affect this relation. Glycogen stores decreased in the presence of halothane and control values were not preserved by the presence of insulin. Lactate production was depressed by halothane in the absence of insulin and was unchanged in the presence of insulin. The ratio of glycolysis to oxygen consumption was increased by halothane both in the presence and absence of insulin. This disparate effect on glucose metabolism, compared with function, may be explained by an inhibition of pyruvate dehydrogenase.

Hypo- and hyperthermia in clinical auditory brain stem response measurement: two case reports.

Two case reports are presented to highlight the important effects of body temperature in clinical auditory brain stem response (ABR) measurement. Case 1 is an 11 year old boy in coma secondary to severe head injury. High dose barbiturate therapy suppressed brain stem neurologic signs and the ABR was relied on as a monitor of CNS status. Hypothermia during this period of intensive care was a crucial factor for meaningful interpretation of ABR findings. The second case was a 26 year old male undergoing hyperthermic therapy for advanced cancer. As body temperature increased from 38 to 42 degrees Centigrade (107.6 degrees Fahrenheit), there was a systematic decrease in latency for waves III and V. An overall hyperthermia-related decrease in the wave I-V latency interval of 0.5 to 0.6 milliseconds was observed on two test dates. ABR results for these two cases are discussed in the context of basic knowledge on body temperature and auditory electrophysiology.

General anesthesia for whole-body hyperthermia.

General anesthesia was used to facilitate 259 whole-body hyperthermia treatments in 90 patients. These patients fell into American Society of Anesthesiologists Classifications 3 (moderate to severe systemic disease) and 4 (severe systemic disease with life-threatening potential). Whole-body hyperthermia imposes severe stress on cardiopulmonary and renal function. In this series, elevation of temperature from 38 degrees to 41.5 degrees raised cardiac output to approximately 200% of control, while oxygen consumption rose 35%. General anesthesia provides conditions which allow for more precise control and support of vital signs, fluid requirements, and blood gases.

Effect of hemorrhagic shock on 5-hydroxytryptamine removal by the lung.

The biogenic amine, radioactive 5-hydroxytryptamine, is removed from the blood during passage through the pulmonary vasculature. After one hour of hemorrhagic shock, the extraction rate increased from 74 to 89 per cent. One and two hours after resuscitation, the lung extracted only 30 per cent of the 5-hydroxytryptamine. The relationship between the pathophysiologic state and altered amine removal is a reflection of prolonged exposure to receptor sites or increased diffusion of serotonin across the endothelium.

Indicator dilution measurement of 5-hydroxytryptamine clearance by human lung.

A double indicator dilution method to measure 5-hydroxytryptamine (5-HT) clearance by lungs of anesthetized patients is described. Immediately after a bolus injection of [3H]dextran and [14C]5-HT into the right atrial port of a Swan-Ganz catheter, blood from the radial artery is fractionated and the tritium and carbon-14 of each fraction is measured. The difference between the normalized curves of dextran and 5-HT vs. time reflect the extent to which 5-HT is extracted by the lung. This method gave a mean value of 61 +/- 3% (n = 10) for extraction of 5-HT, compared to 59 +/- 4% measured simultaneously by means of the pulmonary artery-left atrial gradient of 5-HT. Variations among three successive determinations in each patient made postoperatively were not statistically significant. This technique is applicable whenever Swan-Ganz and radial or brachial artery catheters are placed for routine clinical management and, therefore, may have wide application for measurement of pulmonary amine (or kinin) extraction in conscious human subjects or experimental animals. Because pulmonay clearance may be compromised by endothelial damage, 5-HT extraction measured in this manner could reflect early damage to human pulmonary endothelium--perhaps before clinical evidence of damage, such as interstitial edema and respiratory distress, is evident.

Fate of prostaglandins E(1) and A(1) in the human pulmonary circulation.

It is recognized that the lung extracts norepinephrine and 5-hydroxytryptamine from the pulmonary circulation and that this process is affected by cardiopulmonary bypass. Since alterations in the lung's processing of vasoactive substances may be a mechanism of pulmonary injury sustained during operation, we investigated the lung's ability to extract or metabolize prostaglandin A1 (ga1) and prostaglandin E1 (PGE 1). Sixteen patients undergoing cardiac surgery were studied. In five patients, just before going on bypass, a 10 ml of blood was withdrawn at a constant rate, simultaneously from the pulmonary artery and left atrium. In 11 patients, 3H-PGE1 was injected just prior to bypass and, in five of these, again after coming off bypass. Extraction was calculated from tritium activity in the samples. Metabolites were quantitated by thin-layer chromatography after being identified by marker compounds run simultaneously in each chromatogram. The pulmonary extraction of PGA1 was 11.3 +/- 2.3% and there were no detectable metabolites in left atrial blood. Before bypass the extraction of PGE1 was 42.3 +/- 14.3% and after bypass 24.8 +/- 10.0% (P less than 0.005; Student's paired t test). PGE1 was extensively metabolized with 79.7 +/- 7.1% of total radioactivity appearing in the left atrium as metabolites before bypass and 89.1 +/- 2.0% appearing after bypass. This study indicates that PGA(1) is not metabolized by the lung and is only slightly extracted. On the other hand, PGE(1) is extensively extracted and metabolized. While the rate of metabolism is not significantly affected by cardiopulmonary bypass, the extractiom before bypass was significantly greater than after bypass.

Pulmonary artery flow-guided catheters in the perioperative period. Indications and complications.

The risk factor of pulmonary artery catheterization was assessed in 392 critically ill patients. Major indications for catheterization in the operating room were marginal cardiovascular reserve, anticipated large fluid and blood loss, and hypotensive anesthesia. Immediate complications included cardiac arrhythmia, carotid artery puncture, and pneumotherax. Long-term complications included positive bacterial cultures, pulmonary infarction and neuropathy. None of the complications were directly responsible for the deaths in this series. Pulmonary artery monitoring in critically ill persons is a relatively safe procedure.

5-Hydroxytryptamine extraction by the lung.

Both 5-hydroxytryptamine and norepinephrine are removed from blood during a single passage through the pulmonary vasculature of the dog; 5-hydroxytryptamine is removed to a greater degree than is norepinephrine. The magnitude of extraction of both 5-hydroxytryptamine and norepinephrine is similar to that previously determined in man. In the intact dog, imipramine inhibits the uptake of 5-hydroxytryptamine by the lung in a dose-dependent manner.

Markedly improved pulmonary function after open heart surgery in infancy utilizing surface cooling, profound hypothermia, and circulatory arrest.

The use of surface-induced profound hypothermia with limited cardiopulmonary bypass and circulatory arrest markedly diminished the need for mechanical ventilation for patients undergoing cardiac surgery. Eleven of twenty-two patients were extubated in the operating room and five more patients within 70 minutes postoperatively. Five patients required mechanical ventilation. Four of the five were extubated within 24 hours (mean, 19.05 hours); only one patient required mechanical ventilation greater than 24 hours. This experience would indicate that as the age of surgery is decreased, in conjunction with improved technics of cardiac surgery and anesthesia, the need for mechanical ventilation should be diminished.