Richard L. McCammon

Effects of butorphanol, nalbuphine, and fentanyl on intrabiliary tract dynamics.

The effects of equianalgesk doses of fentanyl citrate (100 μg; n = 20), butorphanol tartrate (2 mg; n = 20), and nalbuphine hydrochloride (10 mg; n=16) on biliary tract dynamics were examined in patients anesthetized with enflurane-nitrous oxide. After removal of the gall bladder, the common bile duct or cystic duct remnant was cannulated with an 18-gauge catheter. Using a modified Caroli apparatus, control measurements of flow through the common bile duct into the duodenum over 60 sec and resting intrabiliary tract pressure were obtained. Patients then were given one of the drugs intravenously and measurements were repeated 5 rain later. Flow rates decreased 35%, 21%, and 13% after fentanyl, butorphanol, and nalbuphine, respectively. Similarly, resting intrabiliary tract pressures increased by 23%, 12%, and 6%, respectively. All changes were statistically significant (P < 0.05) except for the increase in intrabiliary tract pressure after nalbuphine. Likewise, the incidence of decreases in flow rate or increases in intrabiliary tract pressure more than 20% was greater after fentanyl than after either butorphanol or nalbuphine. Agonist-antagonist analgesics may be advantageous in patients with known or suspected biliary tract disease.

Hemodynamic effects of doxacurium chloride in patients receiving oxygen sufentanil anesthesia for coronary artery bypass grafting or valve replacement

Doxacurium chloride is an investigational long-acting neuromuscular blocking drug, which has been shown to be devoid of cardiovascular side effects when administered in modest doses to healthy patients. This is the first hemodynamic study of doxacurium in adult patients with cardiac disease. Forty-one patients scheduled to undergo cardiac surgery were studied. Anesthesia consisted of induction with midazolam 0.2–0.3 mg/kg and sufentanil 0.01–0.03 mg followed by an infusion of sufentanil at 0.03–0.06 mg ± min−1. Baseline hemodynamic data were collected during a stable state of sufentanil anesthesia. Doxacurium was then administered in doses of 1, 2, or 3 times its ED95 of 0.025 mg/kg. Hemodynamic measurements were repeated at 2, 5, and 10 min after doxacurium injection in the absence of surgical stimulation. An additional group of control patients received saline instead of doxacurium. Baseline hemodynamic measurements were similar among groups. There was a slight decrease in heart rate in all groups over time. However, there was no significant difference between the groups of patients receiving doxacurium and the control group in which the heart rate decreased progressively from 52 beats/min at baseline to 49 beats/min 10 min after doxacurium administration. At no time was there any significant change in mean arterial pressure, right atrial pressure, or cardiac output. Likewise derived hemodynamic variables including cardiac index, stroke volume, and pulmonary vascular resistance were unchanged. In addition to the decrease in heart rate, the hemodynamic changes, which reached statistical significance, were clinically insignificant and occurred predominantly in the group of patients receiving doxacurium 0.08 mg/kg. Baseline pulmonary artery occlusion pressure was 13 mmHg, and it increased to 14, 15, and 15 mmHg at 2, 5, and 10 min, respectively. Accordingly, pulmonary vascular resistance fell from 139 dyne · s · cm−5 at baseline to 114, 103, and 102 dyne · s · cm−5 at 2, 5, and 10 min, respectively. There was also a significant increase in stroke volume from 67 to 74 ml at 10 min in this group of patients receiving the largest dose. It is concluded that doxacurium has no clinically significant effect on measured or derived hemodynamic variables at doses up to 3 times its ED95. This combination of a long duration of action and absence of circulatory effects makes doxacurium a potentially useful drug for patients with limited cardiac reserve undergoing prolonged operations.

Pulmonary and systemic vascular responses to nitrous oxide in patients with mitral stenosis and pulmonary hypertension.

Pulmonary and systemic circulatory responses to inhalation of 50% nitrous oxide were studied in 11 patients with pulmonary hypertension prior to elective mitral valve replacement. All patients were premedicated with intramuscular morphine and scopolamine. Compared with awake control measurements while breathing 50% oxygen in nitrogen, heart rate, cardiac index, systemic and pulmonary vascular pressures, systemic vascular resistance, and systemic and pulmonary heart rate, systolic blood pressure products remained unchanged after administration of 50% nitrous oxide for 10 minutes. The only significant change was an increase in pulmonary vascular resistance from 159 ± 18 dynes·sec·cm−5 before nitrous oxide inhalation to 213 ± 27 dynes·sec·cm−5 during nitrous oxide inhalation (p < 0.05). We conclude that nitrous oxide increases pulmonary vascular resistance in patients with preexisting pulmonary hypertension; however, this increase is not associated with alterations in other measured or calculated hemodynamic variables and is probably not of sufficient magnitude to recommend avoiding nitrous oxide in these patients.

Hemodynamic effects of diazepam and diazepam-nitrous oxide in patients with coronary artery disease.

Circulatory responses following intravenous diazepam (0.5 mg/kg) and the subsequent addition of 50% nitrous oxide were studied in 14 patients undergoing elective aortocoronary saphenous vein bypass operations. No patient was receiving propranolol. Preanesthetic medication was with morphine and scopolamine. Diazepam was continuously infused over a 10-minute period. At the conclusion of the infusion, systolic and mean arterial pressures were 13% lower than control awake values (p < 0.05). Heart rate, cardiac output, right a trial pressure, pulmonary arterial pressure, pulmonary artery occluded pressure, and systemic and pulmonary vascular resistance were not changed. The subsequent addition of nitrous oxide resulted in no further statistically significant changes except for a 2.4 torr increase in right a trial pressure (p < 0.05). In contrast, previous data collected from similar patients demonstrated significant reductions in blood pressure and cardiac output while systemic and pulmonary vascular resistance and pulmonary artery occluded pressure were increased when nitrous oxide was added following the administration of morphine (1 to 2 mg/kg). It is concluded that the observed minimal circulatory changes following diazepam administration and the subsequent addition of nitrous oxide make diazepam-nitrous oxide a valuable alternative to a morphine-nitrous oxide induction of anesthesia in patients with coronary artery disease.

Effect of Propranolol on Circulatory Responses to Induction of Diazepam-Nitrous Oxide Anesthesia and to Endotracheal Intubation

The present study evaluated the hemodynamic effects produced by the intravenous infusion of diazepam (0.5 mg/kg over 10 minutes) and the simultaneous inhalation of 50% nitrous oxide in oxygen administered to 19 patients with coronary artery disease who were receiving chronic propranolol therapy (106 ± 67 mg/day). In addition, hemodynamic changes produced by direct laryngoscopy and intubation of the trachea were measured. Data during the induction of anesthesia were compared to measurements obtained in a previously reported group of similar patients anesthetized in the same manner but not receiving propranolol. In the present study, as in previously observed patients not receiving propranolol, induction of anesthesia with diazepam-nitrous oxide did not result in any significant change from awake measurements with respect to heart rate (HR), mean arterial pressure (MAP), or rate-pressure product (RPP). Cardiovascular responses were similar in patients with awake resting heart rates greater than 70 beats per minute (nine patients) and less than 70 beats per minute (10 patients). This suggests that propranolol does not alter the benign hemodynamic effects produced by this type of induction of anesthesia. Laryngoscopy and tracheal intubation significantly (p < 0.01) increased MAP at 1 minute and HR and RPP at 1 and 2 minutes after the start of laryngoscopy. These changes were transient, returning to control values within 3 minutes after intubation. Patients with awake resting HR less than 70 beats per minute had greater increases in HR and RPP at 1 minute than did patients with resting HR greater than 70 beats per minute (p < 0.05). This suggests that propranolol even in doses adequate to produce significant slowing of HR in awake Patients does not ensure protection against increases in HR and MAP associated with laryngoscopy and intubation of the trachea.

Hemodynamic effects of mivacurium chloride administered to patients during oxygen sufentanil anesthesia for coronary artery bypass grafting or valve replacement

The hemodynamic effects of mivacurium chloride were studied in 54 adult cardiac patients anesthetized with midazolam and sufentanil. After baseline data were collected, a placebo (N = 9) or mivacurium was administered over 60 seconds, the latter in doses of 0.15 (N=18), 0.20 (N=18), or 0.25 (N=9) mg/kg. Measurements were repeated 2, 5, and 10 minutes later. Baseline measurements were similar. A slight decrease in heart rate over time reached statistical significance in several groups including the control group. Mean arterial, mean pulmonary arterial, pulmonary arterial occlusion, and right atrial pressures and cardiac output did not change, nor did systemic and pulmonary vascular resistances and cardiac index. Besides the decrease in heart rate, the only hemodynamic change to reach statistical significance was an increase in stroke volume in patients given mivacurium 0.25 mg/kg. Significant hypotension occurred in two patients; in one, a sudden decrease in mean arterial pressure of 24% occurred 1 minute after mivacurium 0.20 mglkg. Blood pressure was restored by ephedrine 10 mg. In the other patient, given mivacurium 0.25 mg/kg, mean arterial pressure decreased 50% from 73 to 37 mm Hg. Recovery was rapid without treatment. It is concluded that mivacurium administered in doses of 0.15 to 0.25 mg/kg over 60 seconds to cardiac patients is associated with few significant hemodynamic effects. However, a small number of patients may experience significant transient hypotension when given doses greater than of 0.15 mg/kg, two times the ED95.

Haemodynamic changes and circulating histamine concentrations following protamine administration to patients and dogs

Haemodynamic changes and the circulating concentrations of histamine associated with the intravenous infusion of protamine were measured in six adult patients undergoing elective aortocoronary bypass graft. surgery and twelve halothane-anuesthetized dogs. Administration of protamine (4.7 mg-kg-1) over five minutes to patients at the conclusion of cardiopulmonary bypass did not produce haemodynamic changes or alterations in the arterial or mixed venous concentrations of histamine, Likewise, the administration of protamine (4.5 mg-kg~’) over five minutes to six dogs produced no haemodynamic changes or alterations in the arterial concentrations of histamine. Conversely, administration of protamine (4.5 tng-kg-1) as a rapid intravenous injection to six other dogs produced a decrease (about 30 per cent below control) in systolic, diastolic and mean arterial pressure (p < 0.05) at 2.5 minutes following the injection. These decreases in blood pressure were paralleled by increases in the arterial concentration of hi stamine from 295 ± 71 pg.(mean ± SD) before protamine to 860 ±6 465 pg.(p < 0.05)2.5 minutes after protamine. Haemo-dynamic changes and the arterial concentration of histamine were not different from control five minutes after protamine administration.It is concluded that administration of protamine over five minutes to patients or dogs does not evoke significant haemodynamic changes or alterations in circulating concentrations of histamine. Conversely, rapid injection of protamine to dogs evokes transient decreases in blood pressure that are paralleled by increases in the arterial concentrations of histamine.RésuméOn a mesuré les répercussions sur l’ hémodynamique et les concentrations plasmatiques d’histamine occasionnées par I’infusion de protamine chez six patients adulles opérés pour aorto-coronarien et chez douze chiens anesthésiés a I’ha/othane.Chez les patients à I’arrêt de la circulation extra-corporelle, I’infusion de protamine (4.7 mgkg-1) n’a en aucun effet sur I’hémodynamique ou les concentrations artérielles et veineuses dhistamine. De la méne façon, I’infusion d’une dose de 4.5 mg-kg-1 de protamine sur une période de cinq minutes chez six chiens n’a en aucun effet. Cependant lorsque la dose a été administrée en injection intraveineuse rapide à six autres chiens, on a observé une réduction de t’ordre de 30 pour cent de la pression artérielle systolique et diastolique et moyenne (p < 0.05)2.5 minutes après I’injection. Ces modifications de pression artérielle s’accompagnaient de facon paral-lile d’une augmentation de la concentration arterielle d’ histamine, concentration qui passait de295 ± 77 pg-ml (M ± DS) à 860 ± 465 pg-ml-1 (p < 0.05) 2.5 minutes apres l’injection. Ces mesures d’ hhnodynamie et d’histamine avaient retrouvé les valeurs de contrôle cinq minutes après léadministration de protamine.On en conclut que l’injection de protamine sur un période de cinq minutes aux patients comme aux chiens ne suscite pas de modifications hémodynamiques notables ou de changements de concentration de I’histamine plasmatique. Cependant, I’injection rapide de protamine chez des chiens provoque une diminution fugace de la pression artérielle, diminution qui s’accompagne de concentration à la hausse d’histamine dans le sang artériel.

Exaggerated Increase in Serum Potassium Following Succinylcholine in Dogs with Beta Blockade

The authors tested in dogs the hypothesis that beta-adrenoceptor blockade might alter the time course or magnitude of serum potassium (K+) changes following the administration of succinylcholine (SCh). The results indicate that the normal increase in K+ induced by SCh (1 mg/kg intravenously) is exaggerated in the presence of propranolol-induced (0.25 mg/kg), beta-adrenoceptor blockade. Specifically, a peak increase of 1.7 mEq/1 (43%) over control K+ was noted in the beta-blocked dogs versus a 0.5 mEq/l (13%) increase in control dogs. The peak increase in K+ occurred later in the beta-blocked dogs (60–90 min post-SCh) versus control dogs (30 min post-SCh). The authors postulate that these results reflect impairment of intracellular uptake of the SCh-induced acute K+ load secondary to beta-adrenoceptor blockade. Additionally, in a third group of dogs, diazepam in a dose of 0.5 mg/kg attenuated the K+ increases (1 mEq/1—24%) following SCh in beta-blocked dogs. Whether these data can be extrapolated to beta-adrenoceptor blocked patients remains a matter for further investigation. In the interim, periodic monitoring of K+ is warranted in any patient receiving medications known to alter the state of activity of the beta-adrenoceptor. In particular, careful consideration must be given to the potential impact of various interventions (SCh administration, K+ infusion) on K+ levels in beta-adrenoceptor blocked patients.