Ceiling respiratory depression by dezocine.

Dezocine in equianalgesic intravenous doses depressed respiratory response to CO2 breathing of six healthy subjects to approximately the same degree as morphine but with a more rapid onset and higher peak depression. The depression was dose related up to 30 mg/70 kg but was not increased by an additional 10 mg/70 kg dose. Its duration of effect was approximately the same as that of morphine. Respiratory depression by dezocine was promptly and almost completely antagonized by 0.4 mg naloxone, but antagonism lasted less than 1 hr. Healthy subjects found dezocine less pleasant than morphine and after large doses reported sensations suggestive of psychotomimetic effects. A ceiling effect for respiratory depression has now been demonstrated for three agonist-antagonist analgesics: nalorphine, nalbuphine, and dezocine. It is not yet clear to what extent this is a general characteristic of agonist-antagonist analgesics.

Comparative respiratory depression of tillidine and morphine.

Respiratory depression induced by tilidine was compared with that of morphine in a crossover study in 6 healthy subjects. Increments of tilidine, 150 mg/70 kg, and morphine, 10 mg/70 kg, were given intravenously and displacement of each subject's CO2 response curve was measured after each dose increment. Both tilidine and morphine caused dose-related displacement of the CO2 response curves to the right. Approximately 80 to 120 mg of tilidine can be expected to induce the respiratory depression of morphine, 10 mg, when given intravenously. Subjective effects after tilidine were qualitatively similar to those of morphine but were of longer duration with nausea and vomiting more frequent. The respiratory depression of both drugs was effectively antagonized by naloxone.

Ceiling effect for respiratory depression by nalbuphine.

The respiratory depressant capacities of intravenous nalbuphine, a potent analgesic of the narcotic antagonist type, and of morphine were compared in 23 healthy subjects using displacement of CO2 response by a steady-state method as the index of respiratory depression. At equianalgesic doses of 10 mg/70 kg, respiratory depression by nalbuphine was equal to that by morphine. When increments of 10 mg/70 kg were given hourly the dose-effect curve for respiratory depression by nalbuphine was flatter than that of morphine, and maximum respiratory depression occurred after 30 mg/70 kg. In a separate study of 10 subjects nalbuphine was administered in 10 mg/70 kg increments to a total dose of 60 mg/70 kg; doses in excess of 30 mg/70 kg failed to increase respiratory depression beyond that induced by morphine 20 mg/70 kg. A ceiling effect for respiratory depression previously known to exist only for nalorphine was thereby demonstrated to apply to nalbuphine. The respiratory depression of nalbuphine was readily antagonized by naloxone 0.4 mg, nalorphine 10 mg, and levallorphan 1.0 mg. Subjective effects of nalbuphine were milder than those of morphine, and dysphoria suggestive of the psychotomimetic effects of narcotic antagonists was reported only 4 times in 24 subject exposures. The ceiling effect for respiratory depression by nalbuphine provides a unique safety factor among potent analgesics.

Venous admixture to radial artery blood samples during cardiopulmonary bypass.

The possibility that venous blood could be withdrawn through a radial artery cannula when venous pressure is high was examined in 30 patients during cardiopulmonary bypass for coronary artery bypass operation. Progressive desaturation of radial artery blood occurred when venous pressure was equal to arterial pressure. Desaturation not only increased with duration of venous obstruction but also occurred immediately if the arterial tree was emptied after occlusion. We believe that these observations result from the transcapillary aspiration of deep venous blood and may produce a potential source of error in measuring arterial oxygen tension during cardiopulmonary resuscitation, cardiac tamponade, and profound right heart failure, as well as cardiopulmonary bypass.

Use of sufficient hemodilution to prevent coagulopathies following surgical correction of cyanotic heart disease.

During surgical correction of cyanotic heart disease with associated polycythemia, sufficient reduction of hemoglobin and hematocrit values has proved effective in preventing postoperative coagulopathies. Three groups of surgical patients were studied: Group I--a control group consisting of 75 adults undergoing uncomplicated correction of acquired heart disease and requiring no blood or blood component transfusion; Group II--15 patients with tetralogy of Fallot whose intraoperative hemoglobin values remained above 10 gm/dl with conventional hemodilution techniques; and Group III--21 cyanotic surgical patients whose intraoperative hemoglobin values were lowered to less than 10 gm/dl with sufficient hemodilution. Group III was further broken down into a subgroup of six patients (Group IIIa) who underwent sequential laboratory determinations, as in Group I. In Group IIIa, postoperative coagulation function tests were only slightly more abnormal than in the nonpolycythemic control group (Group I). Patients in Group III (who had ample hemodilution) experienced 45% less bleeding and required 54% fewer blood components than those in Group II (who underwent conventional hemodilution).

Cardiac operation for congenital heart disease in children of Jehovah's Witnesses.

We reviewed the perioperative courses of 110 children of members of the Jehovah's Witness faith who underwent 112 operations for complete repair of congenital heart disease with cardiopulmonary bypass. Operations were performed over a 20 year period, ending June, 1983. The children ranged in age from 6 months to 12 years and weighed 5.2 to 42.3 kg. Thirty-nine (34.8%) of the patients weighed less than 15 kg, 36 (32.1%) were polycythemic preoperatively, and 26 (23%) had previous thoracic operations. All operations were performed during normothermic cardiopulmonary bypass with a glucose crystalloid prime. No patient received any blood or blood products during hospitalization. Perioperative mortality was 5.4%. Only one of the deaths could be attributed to blood loss. Complications occurred in 10 patients, and none of these could be attributed to failure to transfuse. The results demonstrate that cardiac operations can be safely performed in children denied transfusion and suggest that hemodilution techniques might be used more extensively in children undergoing cardiac operations.

Alteration of coagulation and selected clinical chemistry parameters in patients undergoing open heart surgery without transfusions.

Alteration of coagulation status and certain clinical chemistry laboratory determinations of 75 adult patients undergoing cardiopulmonary bypass procedures for acquired heart disease was studied during and after surgery. None of the patients was given transfusions of blood or blood components. With hemodilution, the mean hematocrit value dropped from 38% to 28% during the procedure. Fibrin degradation products and euglobulin lysis time were transiently abnormal. Factor V diminished somewhat during the procedure, whereas factors VIII and IX increased after surgery. Clottable fibrinogen values decreased slightly, but increased to an abnormally high value at 24 and 48 hours. Mean value of platelet counts decreased from 194,000 to 144,000/microliter immediately after surgery. Knowledge of expected deviation of coagulation factors and certain clinical chemistry tests following open heart surgery is helpful in evaluating the status of the postoperative patient.

Low activated coagulation time during cardiopulmonary bypass does not increase postoperative bleeding.

The activated coagulation time (ACT) is widely used to monitor adequacy of anticoagulation during cardiopulmonary bypass despite absence of data establishing an ACT below which adverse outcomes occur. For anticoagulation before cardiopulmonary bypass, we administered a single dose of heparin (300 U/kg) to 193 patients and measured ACT and heparin levels at intervals after administration. No additional heparin was administered to any patient. Clot formation in the cardiopulmonary bypass circuit and excessive postoperative chest tube drainage were considered outcomes indicating inadequate anticoagulation. Cardiopulmonary bypass averaged 59 +/- 23 minutes (range, 30 to 138 minutes). Activated coagulation time values at every sampling period were normally distributed. In 51 patients (26.4%) ACT values were less than 400 seconds, including 4 less than 300 seconds, at some sampling time after heparinization. Patients with low ACT values did not bleed more postoperatively than those with high ACT values, nor was bleeding related to heparin level. No clots were found in any perfusion circuit. We conclude that a minimum ACT value for adequacy of heparinization is not yet defined but that it is less than 400 seconds.

Addition of papaverine to cardioplegia does not reduce myocardial necrosis.

In a randomized, double-blind prospective study involving 495 patients, we investigated whether the addition of papaverine, 60 mg, to our existing regimen of cold cardioplegia would reduce myocardial necrosis during elective coronary artery bypass operations. Twenty-one (4.2%) patients sustained acute postoperative myocardial infarctions (MI), and 7 (1.4%) died during hospitalization. Neither MI nor death was related to papaverine supplementation. Among 469 patients without postoperative MI, levels of the myocardial-specific isoenzyme of creatine phosphokinase measured 10 hours after aortic cross-clamping were related to ischemic cross-clamp time, but not to papaverine supplementation of cardioplegia. At declamping after completion of distal anastomoses, ventricular fibrillation was more common after cardioplegia without papaverine (32% versus 9%). No other differences between the two groups were found in intraoperative and postoperative hemodynamics, difficulty of weaning from bypass, or postoperative volume requirements. We identified three risk factors for postoperative MI: ECG evidence of new ischemia prior to bypass, unusual technical difficulty with distal anastomoses for the surgeon, and prolonged time of ischemia. We conclude that addition of papaverine to our cardioplegia regimen did not affect outcome or nonspecific myocardial necrosis.

Role of perfusion pressure and flow in major organ dysfunction after cardiopulmonary bypass.

The role of perfusion pressure and flow during cardiopulmonary bypass with moderate hypothermia and hemodilution in the development of new postoperative renal or clinically apparent cerebral dysfunction was examined in 504 adults. Cardiopulmonary bypass flow was targeted at greater than 40 mL.kg-1.min-1 and pressure at greater than 50 mm Hg. Flows and pressures less than target occurred in 21.6% and 97.1% of patients, respectively. Fifteen patients (3.0%) suffered new renal and 13 (2.6%) new central nervous system dysfunction. Low pressure or flow during cardiopulmonary bypass, expressed in absolute values or in intensity-duration units, were not predictors of either adverse outcome. Multivariate analysis identified use of postoperative intraaortic balloon counterpulsation (p less than 10(-6], excessive blood loss in the ICU (p less than 10(-4], need for vasopressors before cardiopulmonary bypass (p less than 10(-4], postoperative myocardial infarction (p less than 10(-3], emergency reoperation (p less than 0.002), excessive postoperative transfusion (p less than 0.02), and chronic renal disease (p less than 0.03) as independent predictors of postoperative renal dysfunction. Independent predictors of postoperative central nervous system dysfunction were cardiopulmonary resuscitation in the intensive care unit (p less than 10(-6], intracardiac thrombus or valve calcification (p less than 0.02), and chronic renal disease (p less than 0.03). Age greater than 65 years (40.7% of patients) did not predict either outcome. We conclude that failure of the native circulation during periods other than cardiopulmonary bypass rather than the flows and pressures considered here is the major cause of renal and clinically apparent central nervous system dysfunction after cardiac operations.

Low ceiling respiratory depression by ciramadol.

Ciramadol, an agonist-antagonist analgesic of lesser milligram potency than morphine, given intravenously at 30 mg/70 kg produced respiratory depression equivalent to that observed with morphine 10 mg/70 kg. Respiratory depression was measured in terms of drug induced displacement of the carbon dioxide response curve of healthy volunteers. In contrast to the progressive respiratory depression by each 10 mg/70 kg increment of morphine, further doses of ciramadol up to 90 mg/70 kg failed to increase respiratory depression. The ceiling of respiratory depression by ciramadol was half the ceiling previously demonstrated for nalbuphine and dezocine. Ceiling respiratory depression may be a general characteristic of agonist-antagonist type analgesics in contrast to pure agonist analgesics.

Ventilation during transport of postoperative patients: comparison of methods.

Changes in arterial blood gases as a result of transporting 28 stable postoperative cardiovascular surgical patients to the intensive care unit were studied. Three methods of ventilation during the 3-minute transport period were compared. All patients were ventilated with 100% oxygen prior to transport. Nine patients were ventilated with air by a self-inflating, non-rebreathing bag. Ten patients were not ventilated at all. Nine patients were ventilated with oxygen in a closed rebreathing circuit constructed from disposable portions of the anesthesia circuit. Oxygen tension on arrival in the intensive care unit was highest in the group ventilated with the closed rebreathing circuit and lowest in the group ventilated with room air. Carbon dixoide tension rose 6.2 mm Hg/min in unventilated patients, 3.2 mm Hg/min in patients ventilated with the closed rebreathing circuit, and did not change in the group ventilated with air. We conclude that stable patients can be safely transported while breathing air for 3 minutes. For longer periods of transport, the closed rebreathing circuit provides high oxygen tension with acceptable hypercarbia and provides a convenient alternative to the use of portable oxygen tanks.

Methemoglobinemia diagnosed as a consequence of cardiopulmonary bypass.

Clinically significant methemoglobinemia is rare and difficult to diagnose when other causes of cyanosis are likely. We report a patient in whom unstable angina pectoris and chronic obstructive pulmonary disease were assumed to be responsible for preoperative cyanosis. The use of cardiopulmonary bypass for aortocoronary grafting enabled the clinical diagnosis of methemoglobinemia to be made.

Unaccounted blood loss in operations using cardiopulmonary bypass.

Typically, blood loss after operations requiring cardiopulmonary bypass is estimated from the sum of blood on sponges and drapes, in the suction system reservoir, and in chest drainage bottles. Prime of the extracorporeal circuit is usually returned to the patient, but no accounting is made of blood remaining in the circuit. In 50 patients, we examined 25 bubble and 25 membrane oxygenator circuits after completion of cardiopulmonary bypass and after return of all prime to the patients. Saline solution was added to each circuit and recirculated for 3 minutes, after which the volume and hematocrit of the recirculated saline were determined. From these values, we estimated that 92.0 +/- 18.1 mL of red blood cells remained in the bubble oxygenators and 100 +/- 11.6 mL in the membrane oxygenators. This volume of red cells is equivalent to 250 mL of whole blood with 35% hematocrit or 30 grams of hemoglobin at 12 gm% concentration. We conclude that blood loss after operations requiring cardiopulmonary bypass is systematically underestimated by the approximately 250 mL left as red cells on the walls and filters of the extracorporeal circuit after return of all prime to the patient.