Enoxaparin for unstable angina and ancrod for cardiac surgery following heparin allergy.

OBJECTIVE: To describe a patient who presented with heparin allergy and required alternate anticoagulation for unstable angina and coronary artery bypass surgery. To review therapeutic alternatives to porcine heparin for patients with hypersensitivity or intolerance to standard heparin anticoagulation. CASE SUMMARY: A 74-year-old man with a 15-year-old coronary artery bypass graft presented to the emergency room with unstable angina and was scheduled for urgent coronary artery revascularization. A bolus dose of porcine heparin was administered followed by a continuous infusion. Shortly afterward the patient developed a type I allergic reaction to the porcine heparin that was confirmed by rechallenge. Three alternatives to porcine heparin were tried, including bovine lung heparin, low-molecular-weight heparin (enoxaparin), and ancrod. The patient was found to be cross-sensitive to bovine lung heparin, but tolerated enoxaparin for unstable angina without cross-sensitivity. Anticoagulation for cardiopulmonary bypass was achieved with an infusion of ancrod that was later reversed with cryoprecipitate. The patient was discharged postoperatively on day 5 without the complication of excessive bleeding. DISCUSSION: Type I allergic reaction to unfractionated heparin is a rare occurrence and could be the result of a variety of factors. Possible causes for the reaction include a porcine protein, a preservative contained in the heparin solution, or a hapten formed between heparin and a plasma protein. We considered four alternatives to heparin anticoagulation: rush desensitization, bovine lung heparin, low-molecular-weight heparin, and ancrod. The patient was cross-sensitive to bovine lung heparin, but was able to tolerate low-molecular-weight heparin (enoxaparin). This was unexpected because enoxaparin is derived from unfractionated porcine heparin. Testing for cross-sensitivity had no value in this case, as two negative subcutaneous test doses were followed by dramatic reactions when the drugs were given intravenously. Although enoxaparin has been used for anticoagulation during bypass surgery, there is more experience with ancrod as an alternative to heparin. Repeat bypass surgery, which normally results in above-average blood loss, was successfully performed with a very low fibrinogen concentration (< 0.15 g/L) during ancrod anticoagulation. CONCLUSIONS: We conclude that ancrod was a safe and effective alternative to heparin for coronary artery bypass surgery in this patient in whom a heparin product had caused a hypersensitivity reaction. We discovered on two occasions that a negative subcutaneous test dose for heparin allergy did not predict a severe type I allergic reaction when the heparin was later administered intravenously. Furthermore, we found that a low-molecular-weight heparin administered subcutaneously for a short period of time did not cause cross-sensitivity in a patient with a type I allergy to unfractionated heparin.

A trial of desmopressin (1-desamino-8-D-arginine vasopressin) to reduce blood loss in uncomplicated cardiac surgery.

Previous studies have suggested that desmopressin may reduce the bleeding diathesis that often complicates open-heart surgery. To pursue this question further, we performed a double-blind, randomized, placebo-controlled trial to determine whether the previously reported beneficial effect of desmopressin on hemostasis during complex cardiac surgery was applicable to all elective cardiac surgical procedures involving cardiopulmonary bypass. In 150 consecutive patients, most of whom underwent primary coronary-artery bypass grafting, we compared the effects of intravenous desmopressin (0.3 microgram per kilogram of body weight) with those of saline placebo on postoperative blood loss and the need to replace blood products. The median amount of blood lost within the first 24 hours after operation was similar in the desmopressin and placebo groups (865 vs. 738 ml; P = 0.26). The postoperative use of blood replacement products did not differ significantly between the groups (1025 ml [95 percent confidence interval, 300 to 4140 ml] in the desmopressin group and 860 ml [247 to 5346 ml] in the placebo group). Desmopressin is believed to exert its hemostatic effect by releasing von Willebrand factor. The level of ristocetin cofactor, a functional index of the level of von Willebrand factor, was increased approximately twofold from base line in both treatment groups 90 minutes and 24 hours after the administration of medication. Similarly, the levels of von Willebrand factor multimers increased uniformly in both groups. These findings may be consistent with a normal stress response of von Willebrand factor to major surgery and could explain our failure to detect a therapeutic effect of desmopressin. We conclude that the majority of patients who undergo elective cardiac surgery receive no hemostatic benefit from the use of desmopressin.

Early extubation after high-dose fentanyl anaesthesia for aortocoronary bypass surgery: reversal of respiratory depression with low-dose nalbuphine.

To investigate the possibility of selective reversal of narcotic-induced respiratory depression following fentanyl anaesthesia, we studied 20 patients after aortocoronary bypass surgery. All patients were anaesthetized with fentanyl, 40 micrograms . kg-1 and oxygen, with isoflurane as indicated. In a random double blind fashion either incremental doses of nalbuphine, or normal saline were administered approximately four hours after cardiopulmonary bypass. Respiratory depression was evaluated using blood gas and end tidal CO2 (PETCO2) measurement, and in addition, a ventilatory response to CO2 was obtained preoperatively and at selected intervals postoperatively. Despite randomization, patients with more respiratory depression were assigned to nalbuphine. There appeared to be a reversal of respiratory depression with nalbuphine, indicated by a fall in the resting PETCO2 value. This apparent reversal of respiratory depression was associated with a significant increase in pain, requiring treatment in three patients. We conclude that low-dose nalbuphine is not an acceptable method of antagonism of respiratory depression in this group of patients. Many patients who did not receive nalbuphine were able to breathe adequately at an earlier stage than was previously suspected. Close monitoring of the respiratory system may permit earlier extubation without the requirement of a narcotic antagonist after this dose of fentanyl.

Effect of heated humidified gases on temperature drop after cardiopulmonary bypass.

In an attempt to prevent the decrease in nasopharyngeal temperature (NPT) ("afterdrop") after cardiac surgery, 30 patients undergoing hypothermic cardiopulmonary bypass (CPB) were randomly assigned to receive humidified heated inspired gases at 45 degrees C at the proximal end of the endotracheal tube (group I) or dry gases at room temperature (group II), from the time of termination of CPB. All patients received high flow rates on CPB during the rewarming period with the use of vasodilator drugs when necessary. Both groups were comparable with respect to total bypass time, rewarming time, and temperature at termination of CPB. In addition, the NPT was compared with the tympanic membrane temperature (TMT) in group I to assess the validity of the NPT under these conditions. The results indicate that heating and humidifying inspired gases do not prevent afterdrop and do not falsely increase the nasopharyngeal temperature. The reasons for the ineffectiveness of heated humidified gases may include a large heat deficit at termination of CPB despite a normal NPT, and the very small heat content of heated gases. Monitoring the temperature of a site that reflects the heat deficit, and a more complete rewarming during CPB are suggested as a better approach to the prevention of afterdrop.

Role of renin-angiotensin system in cardiopulmonary bypass hypertension.

The role of the renin-angiotensin system in the aetiology of perioperative hypertension was studied in 15 previously normotensive patients undergoing coronary artery surgery and anaesthetized with fentanyl. Measurements of plasma renin activity were made at intervals before and during cardiopulmonary bypass (CPB). In addition, angiotensin II blockade with saralasin was used in an attempt to treat hypertension during CPB. Nine of the patients became hypertensive (increase in systemic pressure of more than 20 per cent) before CPB and although the mean plasma renin activity was higher in this group than in the normotensive patients it was within normal limits for each group. Hypertension during CPB (mean blood pressure greater than 100 mmHg at 1.8 l X m-2 flow), occurred in seven patients but was not associated with increased renin activity and did not respond to saralasin in doses up to 20 micrograms X kg-1 X min-1. It is concluded that cardiopulmonary bypass associated hypertension is not mediated by activation of the renin-angiotensin system.

Narcotic requirements for intravenous anesthesia.

MAC BAR, the minimum end-tidal alveolar anesthetic concentration that inhibits adrenergic response to a noxious stimulus in 50% of subjects, is a quantifiable physiological parameter that can be used to determine potency and therapeutic indices of volatile anesthetics. We wished to determine whether there is a minimal intraarterial plasma concentration (MIC BAR) of an opiate such as fentanyl that will prevent a hypertensive response to noxious stimuli in 50% of patients undergoing aortocoronary bypass surgery (ACBP). Forty-three patients with good left ventricular function were studied. All patients were premedicated with diazepam, morphine, and scopolamine. Five groups of patients were anesthetized with different fentanyl anesthesia protocols, each designed to produce different plasma fentanyl concentrations (PFC). A 20% increase in systolic blood pressure compared to control was considered an adrenergic response that related to the plasma fentanyl concentration inferred from each patient's PFC time-concentration curve. Only four patients became hypertensive with a PFC greater than 20 ng/ml. One patient became hypertensive at intubation with a PFC of 12.3 ng/ml. There was no statistically significant difference in the mean PFC in patients who became hypertensive at each event. During aortic dissection, when significantly more patients became hypertensive, there was no difference in the incidence of hypertension in patients with a PFC above or below 20 ng/ml. Two patients became hypertensive at skin incision with a PFC over 30 ng/ml. A MIC BAR could not be identified because of the great variability in the PFC of patients who became hypertensive.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood pressure response and plasma fentanyl concentrations during high- and very high-dose fentanyl anesthesia for coronary artery surgery.

We examined whether different plasma fentanyl concentrations could maintain hemodynamic stability during coronary artery surgery. Two randomly selected groups of 10 patients were studied. Patients in group 1 received a single 75-micrograms/kg intravenous dose of fentanyl; patients in group 2 received the same dose but it was followed by an infusion of fentanyl at a rate of 0.75 micrograms/kg/min. The total dose of fentanyl in group 2 was 162 +/- 6.5 micrograms/kg (mean +/- SEM). At some point during surgery, all 10 patients in group 1 and 7 of 10 patients in group 2 had a hypertensive response. Plasma fentanyl concentrations in the two groups were not significantly different in the period 10-45 min after induction of anesthesia. At 60 min, corresponding to the time of aortic root dissection, mean plasma fentanyl concentration was statistically significantly lower in group 1 than in group 2 (13.5 +/- 1.4 ng/ml and 24 +/- 2.3 ng/ml, respectively, P less than 0.01). However, no significant difference was observed in the frequency of hypertensive response between the two groups in the period before cardiopulmonary bypass. During cardiopulmonary bypass, plasma fentanyl concentrations in group 1 were 2-3 times lower than those in group 2, and hypertension was observed in all 10 patients in group 1 but in only 2 patients in group 2 (P less than 0.05). Patients in group 1 were ventilated for 16.6 +/- 1.5 h, and those in group 2 for 19.1 +/- 1.8 h, postoperatively (P greater than 0.05). Six patients in group 1 required vasodilating drugs, whereas eight patients in group 2 required alpha-adrenergic agonists. Although the plasma fentanyl concentrations achieved were not successful in totally suppressing a hypertensive response, this study suggests that a plasma fentanyl concentration might be attainable to effect this.

A profile of intravenous nitroglycerin use in cardiopulmonary bypass surgery.

We studied the indications for use, time to onset of effect, approximate effective concentration and therapeutic success of commercially prepared intravenous nitroglycerin (NTG) in 50 patients undergoing cardiopulmonary bypass (CPB) surgery. Nitroglycerin was used to treat systemic or pulmonary hypertension, myocardial ischaemia and ventricular failure. Twenty-one patients had more than one indication for NTG use. Nineteen of 22 patients with pulmonary hypertension, 12 of 13 patients with ischaemic changes, and 13 of 15 patients with ventricular failure improved during intravenous NTG administration. Hypertension during CPB was ameliorated in only six of ten instances. The time to onset of effect ranged from 4.1 +/- 0.8 to 7.8 +/- 2.8 minutes and the mean approximate effective NTG concentration varied from 1.7 +/- 0.3 to 2.9 +/- 0.7 micrograms . kg-1.min-1 (doses only approximate due to our use of an infusion system which absorbs NTG). Complications from intravenous NTG administration were not seen. We conclude that this NTG preparation facilitates treatment of prebypass hypertension, pulmonary hypertension, myocardial ischaemia and ventricular failure but is less effective for the treatment of hypertension during CPB.

Fentanyl infusion anesthesia for aortocoronary bypass surgery: plasma levels and hemodynamic response.

Plasma fentanyl concentrations were measured by radioimmunoassay in patients during aortocoronary bypass surgery and correlated with hemodynamic responses to surgical stimulation. Thirty patients scheduled for aortocoronary bypass surgery were divided into three groups of 10. Patients in group 1 received fentanyl, 30 micrograms/kg, as a loading dose followed by an infusion of 0.3 microgram/kg/min; those in group 2 received 40 micrograms/kg as a loading dose followed by an infusion of 0.4 microgram/kg/min; and those in group 3 received 50 micrograms/kg as the loading dose followed by an infusion of 0.5 microgram/kg/min. The total dose of fentanyl administered to each group up to the time of rewarming on cardiopulmonary bypass was 60 micrograms/kg, 90 micrograms/kg, respectively. Each of the dose regimens produced stable plasma concentrations starting approximately 20 minutes after induction and continuing until the infusion was discontinued. Patients in group 1 had a mean plasma concentration of 10 to 12 ng/ml in the stable period compared with 12 to 14 ng/ml in group 2 and 15 to 18 ng/ml in group 3. Fewer patients in group 3 responded to intubation and surgical stimulation than in the other groups, although the differences between groups were not statistically significant. Response to stimulation was treated by the administration of droperidol or volatile anesthetic agents. At a plasma concentration of 15 ng/ml, 50% of patients had an increase in systolic blood pressure which required treatment. This minimal intra-arterial concentration, analogous to MAC, can be achieved by the administration of fentanyl as a loading dose of 50 micrograms/kg followed by an infusion of 0.5 microgram/kg/min.