Norman R. Searle

Propofol in patients with cardiac disease

Propofol is an intravenous anaesthetic which is chemically un-related to other iv anaesthetics. Most anaesthetists are now becoming familiar with propofol’s pharmacokinetic and pharm-acodynamic properties. It has proved to be a reliable drug that can be used safely for induction and maintenance of anaesthesia for most surgical procedures and unlike other anaesthetic agents, it can especially be extended into the postoperative setting or intensive care unit for sedation. Propofol’s greatest attributes are its pharmacokinetic properties which result in a rapid, clear emergence and lack of cumulative effects even after prolonged administration. Compared with other iv anaesthetics, the induction dose of propofol has a relatively higher incidence of respiratory depression, short-lived apnoea and blood pressure reduction that may occasionally be marked. Possible mechanisms for the hypotension may relate to (1) its action on peripheral vasculature (vasodilatation), (2) decreased myocardial contractility, 3) resetting of the baroreflex activity and (4) inhibition of the sympathetic nervous system outflow. In vitro studies indicate that propofol depresses the immunological reaction to bacterial challenge as well as the chemotactic activity. Clinical studies, in cardiac surgery, have demonstrated that propofol, in association with an opioid, is a logical anaesthetic choice. Propofol is about to receive approval for continuous iv sedation. Comparative studies of propofol and midazolam have clearly demonstrated the superiority of propofol in terms of rapid recovery and precise control of the level of sedation.RésuméLe propofol est un nouvel agent anesthésique iv qui se distingue des autres agents par sa structure chimique. Les anesthésistes sont maintenant familiers avec les propriétés pharmacocinétiques et pharmacodynamiques du propofol. Il s’est révélé efficace et sécuritaire comme agent d’induction et de maintien de l’anesthésie pour diverses procédures chirurgicales. Contrairement aux autres anesthésiques iv, le propofol peut être retenu comme agent de sédation en période postopératoire ou pour faciliter la ventilation mécanique aux soins intensifs. Ses atouts principaux relèvent de ses propriétés pharmacocinétiques qui expliquent sa rapidité d’émergence et l’absence d’accumulation même à la suite d’une administration prolongée. En contrepartie, le propofol occasionne une plus grande incidence de dépression respiratoire, d’apnée et une chute de la tension artérielle qui, occasionnellement, peut être sévère. Les mécanismes probables pour expliquer cette chute de tension sont: 1) la vasodilatation périphérique (diminution des résistances périphériques), 2) la diminution de la contractilité myocardique, 3) un réajustement de l’activité des barorécepteurs et 4) une inhibition du système nerveux sympathique. Une dépression du système immunitaire peut se manifester à la suite d’une infusion prolongée. Des études in vitro suggèrent une dépression de la réponse immunologique ainsi qu’une diminution de la réponse chémotactique des leucocytes. Des études cliniques chez des patients subissant une chirurgie cardiaque ont démontré que le propofol, en association avec un opiacé, est une alternative anesthésique acceptable. Le propofol va recevoir l’approbation pour l’administration intraveineuse continue à visée sédative. Des études comparatives entre le propofol et le midazolam ont démontré la supériorité du propofol en termes de rapidité de récupération de l’anesthésie et du contrôle précis du niveau de sédation.

Propofol or midazolam for sedation and early extubation following cardiac surgery

PurposeThe purpose of this randomized, double-blind study was to evaluate the efficacy of midazolam and propofol for postoperative sedation and early extubation following cardiac surgery.MethodsASA physical status II-III patients scheduled to undergo elective first-time cardiac surgery with an ejection fraction > 45% were eligible. All patients received a standardized sufentanil/isoflurane anaesthesa. Dunng cardiopulmonary bypass 100 μg · kg−1· mm−1 propofol was substituted for isoflurane. Upon amval in the Intensive Care Unit (ICU). patients were randomized to either 10 μg · kg · min−1 propofol (n = 21) or 0.25 μg · kg · mm−1 midazolam (n = 20). Infusion rates were adjusted to maintain sedation within a predetermined range (Ramsay 2–4). The infuson was terminated after four hours. Patients were weaned from mechanical ventilation and their tracheas extubated when haemodynamic stability, haemostasis, normothermia and mental orientation were confirmed. Haemodynamic measurements, artenal blood gas tensions and pulmonary function tests were recorded at specified times.ResultsThere were no differences between the two groups for the time spent at each level of sedation, number of infusion rate adjustments, amount of analgesic and vasoactive drugs, times to awakening and extubation. The costs of propofol were higher than those of midazolam. There were no differences in haemodynamic values, artenal blood gas tensions and pulmonary function.ConclusionWe conclude that midazolam and propofol are safe and effective sedative agents permitting early extubation in this selected cardiac patient population but propofol costs were higher.RésuméButLe but de cette étude randomisée, à double insu était d’évaluer l’efficacité du midazolam et du propofol pour sédation postopératoire en vue d’une extubation précoce postchirurgie cardiaqueMéthodologieTout patient ASA II-III admis pour une première chirurgie cardiaque élective ayant une fraction d’éjection > 45% était éligible. Tous les patients ont reçu une anesthésie standard à base de sufentanil/isoflurane. Durant la circulation extracorporelle, le propofol (100μg · kg−1· min−1) a été substitué à l’isoflurane. Dès l’arnvée aux soins intensifs, les patients furent randomisés soit au propofol (n = 21)à 10 μg · kg−1· mm−1 sort au midazolam (n = 20) 0.25 μg · kg−1· mm−1. Les débits de perfusion étaient ajustés pour maintenir un niveau de sédation prédéterminée (Ramsay 2–4). La perfusion était cessée après quatre heures. Les patients étaient sevrés de la ventilation mécanique et extubés lorsque la stabilité hémodynamique, l’hémostase, la normothermie et l’orientation mentale étaient confirmées. Des bilans hémodynamiques, gaz arténels et fonction pulmonaire furent enregistrés à des intervalles spécifiques.RésultatsIl n’y avait pas de différence entre les groupes pour le temps occupé aux différents niveaux de sédation, d’ajustement de perfusion, le temps d’éveil et d’extubation. Le coût du propofol était plus élevé que celui du midazolam. La demande d’analgésique et l’utilisation d’agents vasoactifs étaient similaires. Aucune différence de fonction pulmonaire, gaz arténels et hémodynamique n’a été décelée.ConclusionNous concluons que le midazolam et le propofol sont sécuritaires et efficaces comme agents de sédation permettant une extubation précoce pour ce groupe de patients cardiaques sélectionnés mais le coût du propofol est plus élevé.

Hydromorphone patient-controlled analgesia (PCA) after coronary artery bypass surgery

We conducted a study to compare the effectiveness of patientcontrolled analgesia (PCA) technique to conventional analgesic therapy (CAT) after coronary artery bypass graft (CABG). The PCA group received hydromorphone 0.1 mg · hr−1 basal infusion and bolus doses of 0.2 mg Q 5 min (maximum 1.2 mg · hr−1) while the CAT group received morphine 2.5 mg iv Q 30 min prn until extubation followed by prn meperidine 1 mg · kg−1 im Q4 hr or acetaminophen 325 mg with codeine 30 mg po (1 or 2 tablets) when oral intake was possible. The degree of pain was assessed using a Visual Analogue Scale (VAS) starting after extubation and every 6–8 hr for the next 60 hr. Holter monitoring was initiated one hour after patient arrival in the Intensive Care Unit (ICU) and continued for 72 hr. Other measured variables were pulmonary function, sedation, side effects and total opioid requirements. Results show that the day-to-day VAS pain score decreased in the PCA group (P < 0.001) while it remained unchanged in CAT patients. The PCA patients had lower VAS pain scores at extubation (P < 0.05). During the third postoperative day, the PCA group had a lower VAS pain score, a lower incidence of severe pain defined as a score > 5 on the VAS scale, and a reduced incidence of myocardial ischaemia (P < 0.01). However, there was no difference in the duration, severity, area under the curve (AUC), or heart rate during ischaemic events. Postoperative pulmonary function was abnormal in both groups (NS) with minimal recovery by the fourth day. Opioid requirements, incidence of side effects and the degree of sedation were similar. We conclude that the PCA technique for analgesia provided slightly better results. The finding of a reduced incidence of myocardial ischaemia in the PCA group warrants further clinical investigation.RésuméNous avons effectué une étude comparative sur l’efficacité de l’analgésie contrôlée par le patient (PCA) par rapport au traitement analgésique conventionnel (CAT) chez des patients subissant une chirurgie de revascularisation myocardique. Après randomisation, le groupe PCA (n = 30) recevait une perfusion continue d’hydromorphone (0.1 mg · hr−1) avec des bolus de 0.2 mg Q 5 min (maximum 1.2 mg · hr−1), alors que le groupe CAT (n = 30) recevait morphine 2.5 mg iv Q 30 min prn jusqu’à l’extubation, suivie par mépéridine 1 mg · kg−1 im Q 4 hr prn ou acétaminophène 325 mg avec codéine 30 mg po (1–2 comprimés) lorsque le patient pouvait s’alimenter. La perception de douleur fut évaluée à l’aide d’une échelle visuelle analogique (VAS) lorsque le patient fut extubé et à toutes les 6–8 hr pendant 60 hr. Un monitorage Holter de 72 hr fut débuté 1 hr après l’arrivée du patient aux soins intensifs. L’étude a aussi évalué les changements dans la fonction pulmonaire, la sédation, les effets secondaires et la quantité d’opiacés requise. Nos résultats démontrent que le degré de sévérité de la douleur a diminué significativement d’une journée à l’autre dans le groupe PCA (P > 0.001) comparativement au groupe CAT A l’extubation, les patients PCA avaient moins de douleur (P < 0.05). Au troisième jour postopératoire, le groupe PCA avail moins de douleur (P < 0.05), aucune incidence de douleur sévère (P < 0.01) et une incidence diminuée d’ischémie myocardique (P < 0.01). Toutefois, il n’y avail pas de différence dans la durée, l’intensité, la surface sous la courbe (AUC) et la fréquence cardiaque pendant les épisodes d’ischémie myocardique. La fonction pulmonaire postopératoire était anormale dans les deux groupes (P = NS) avec très peu de récupération après quatre jours. Les besoins en opiacés, l’incidence des effets secondaires et le degré de sédation étaient similaires. Nous concluons que la technique de PCA procure une analgésie légèrement supérieure. Le fait qu’il y avail une diminution dans l’incidence d’ischémie myocardique dans le groupe PCA nécessite d’autres investigations cliniques.

Amrinone, in combination with norepinephrine, is an effective first-line drug for difficult separation from cardiopulmonary bypass

A crucial element for weaning patients from cardiopulmonary bypass (CPB) rests on the selection of an appropriate therapeutic regimen. Amrinone, a phosphodiesterase III inhibitor, combines inotropic support with pulmonary and systemic vasodilatation, without increasing heart rate (HR) or myocardial oxygen consumption. These characteristics should be useful in the failing heart during weaning from CPB. Nineteen patients were included in this prospective, open-labelled, phase IV study when systolic blood pressure (SBP) <80 mmHg, and diastolic pulmonary artery pressure (DPAP) > 15 mmHg or central venous pressure (CVP) > 75 mmHg, during progressive separation from CPB. At that moment, CPB flow was increased to alleviate heart failure and amrinone administered as a bolus (0.75 mg · kg−1) followed by an infusion (10 μg · kg−1 · min−1). Weaning from CPB was then resumed and haemodynamic variables (SBP, DPAP, CVP and HR) were compared with those measured at CPB flow when failure had first occurred. Failure to wean from CPB occurred at 57 ± 25% of full pump flow. After the amrinone bolus, DPAP and CVP decreased by 20% and 21% respectively. Subsequently, 16 patients required the infusion of norepinephrine (4-8 fig-min−1) to maintain a SBP > 80 mmHg. Heart rate remained unchanged after the bolus of amrinone, after separation from CPB, and no arrhythmias were noted. Successful weaning from CPB was possible 12 ± 8 min after the amrinone bolus. Weaning resulted in a cardiac index similar to that measured pre-bypass. Amrinone is rapidly effective during weaning from CPB and, in combination with norepinephrine, provides the necessary inotropic support during this unstable period.RésuméLorsque le sevrage de la circulation extracorporelle (CEC) s’avère difficile, le choix d’un régime thérapeutique approprié est d’une importance capitale. L’amrinone, un inhibiteur de la phosphodiestérase de type III, augmente l’inotropie et dilate les circulations pulmonaire et systémique, sans augmenter la fréquence cardiaque ou la consommation d’oxygène du myocarde. Ces caractéristiques pharmacologiques devraient être bénéfiques durant le sevrage de la CEC. Furent inclus dans cette étude prospective de phase IV dix-neuf patients dont la pression artérielle systémique (PAS) était <80 mmHg alors que la pression diastolique de l’artère pulmonaire (PDAP) > 15 mmHg ou la pression veineuse centrale > 15 mmHg durant le sevrage lent et progressif de la CEC. Lors de l’échec du sevrage, le débit de la CEC était augmenté de façon à soulager la défaillance cardiaque et un bolus damrinone était administré (0.75 mg · kg−1), suivi d’une perfusion (10 μg · kg−1 · min−1). Le sevrage était alors repris et les paramètres hémodynamiques comparés au débit de CEC où l’échec était survenu initialement. L’échec du sevrage survint à 57 ± 25% du plein débit de CEC. Après le bolus d’amrinone, la PDAP et la PVC diminuèrent de 20% et de 21% respectivement. Par la suite, une perfusion de norépinéphrine (4–8 μg · min−1) fut requise chez 16 patients afin de maintenir la PAS > 80 mmHg. Le rythme cardiaque demeura stable après l’administration du bolus d’amrinone et après le sevrage de la CEC, et aucune arythmie ne fut notée. Les patients furent complétement sevrés de la CEC 12 ± 8 min après le bolus d’amrinone et leur index cardiaque après la CEC était superposable à celui mesuré avant la CEC. Ainsi, l’amrinone agit rapidement et efficacement durant le sevrage de la CEC et, en association avec la norépinéphrine, procure au myocarde le support inotrope nécessaire durant cette période de grande instabilité hémodynamique.

Cardioplegic arrest with l-arginine improves myocardial protection: results of a prospective randomized clinical trial

BACKGROUND Blood cardioplegic arrest remains the method of choice for myocardial protection. L-arginine has been suggested to improve protection through an increase in nitric oxide production. METHODS A prospective, randomized, double-blinded clinical trial comparing standard blood cardioplegic solution to L-arginine-enriched solution (7.5 g/500 mL) enrolled 200 patients undergoing coronary artery bypass grafting. Clinical data and biochemical markers of ischemia were recorded. Warm blood cardioplegia (33 degrees C) was administered in 74% of patients and cold blood (20 degrees C) was used in 26% of patients. Both groups averaged three grafts per patient. RESULTS There were two (2%) deaths in both groups. There were four (4%) myocardial infarctions (MI) in the control group and six (6%) infarctions in the L-arginine group (p = 0.5). For the 190 patients without MI, serum levels of troponin T averaged 0.40+/-0.43, 0.38+/-0.42, and 0.39+/-0.50 microg/L in control patients compared with 0.28+/-0.22, 0.24+/-0.18, and 0.27+/-0.20 microg/L in L-arginine patients, respectively, 12, 24 and 48 hours after coronary artery bypass grafting (p = 0.03). The cardiac index averaged 2.7+/-0.8 L x min(-1) x m(-2) in control patients and 2.9+/-0.7 L x min(-1) x m(-2) in arginine patients immediately after surgery (p = 0.09). Intensive care unit and hospital length of stay averaged 3.5+/-5 days and 7.3+/-6 days in control patients compared with 2.5+/-3 days and 6.1+/-4 days in arginine patients (p = 0.09). CONCLUSIONS L-arginine-supplemented blood cardioplegic solution is associated with reduced release of biochemical markers of myocardial damage, suggesting improved myocardial protection.

Does retrograde administration of blood cardioplegia improve myocardial protection during first operation for coronary artery bypass grafting

BACKGROUND The objective of this study was to evaluate the value of retrograde blood cardioplegia in coronary artery bypass grafting. METHODS In 1994 and 1995, 224 patients undergoing first-time isolated coronary artery bypass grafting were randomized to antegrade (112 patients, group 1) or retrograde (112 patients, group 2) administration of blood cardioplegia. In group 1, 76 patients were given warm cardioplegia (at 33 degrees C) and 36 had cold cardioplegia (< 20 degrees C), whereas in group 2 cardioplegia was warm in 77 patients and cold in 35. The two randomization groups had similar demographic and angiographic characteristics. The number of grafted coronary arteries averaged 2.9 +/- 0.7 in group 1 and 2.8 +/- 0.7 in group 2. Total duration of cardiopulmonary bypass (78 +/- 23 and 75 +/- 21 minutes) and of aortic cross-clamping (47 +/- 16 and 46 +/- 16 minutes), total volume of infusion of the crystalloid component of cardioplegia (988 +/- 297 and 1016 +/- 595 mL), and total duration of infusion of cardioplegia (23 +/- 10 and 22 +/- 11 minutes) were similar (p > 0.05). RESULTS There was no death in group 1 and one in group 2 as a result of a pulmonary embolus, for a global early mortality of 0.45%. The numbers of perioperative myocardial infarction (5 versus 3), congestive heart failure (4 versus 5), postoperative hemorrhage (4 versus 4), and stroke (1 versus 2) were also similar (p > 0.05). Release curves of total creatine kinase, creatine kinase-MB by serum activity and mass concentration, and troponin T were not significantly different (p > 0.05) between the two groups. For the 216 patients without perioperative myocardial infarction, peak enzyme release of creatine kinase-MB at 24 hours averaged 23 +/- 22 and 20 +/- 18 IU/L, and that of troponin T averaged 1.1 +/- 1.1 and 1.3 +/- 1.5 micrograms/L at 6 hours for the antegrade and the retrograde groups, respectively (p > 0.05). CONCLUSIONS Our results indicate no evidence that the retrograde method of cardioplegic infusion improves myocardial protection during first operation for isolated coronary revascularization compared with the usual antegrade route.

Assessment of the arterial tonometer (N-CAT) for the continuous blood pressure measurement in rapid atrial fibrillation.

The N-CAT is a newly developed arterial tonometer (TBP) able to determine systolic, diastolic and mean arterial blood pressures continuously and noninvasively. The aim of this study was to evaluate the accuracy and reliability of TBP relative to directly measured invasive blood pressure (IBP) in ten haemodynamically stable postoperative cardiac patients who were in rapid atrial fibrillation (HR ≥ 100 bpm). There were differences between TBP and IBP for systolic (−1.7 mmHg) and diastolic (+0.9 mmHg) values but not for the mean arterial blood pressures. The N-CAT was able to follow blood pressure changes closely and demonstrated an average systolic, diastolic and mean bias (±SD) of −1.71 ± 4.6, 0.99 ± 4.6 and 0.33 ± 4.2 mmHg, respectively. Although these biases are within the required standards for equivalency for noninvasive blood pressure to invasively determined blood pressure, approximately 20% of the readings were > ±10 mmHg while only 5% were > ±20 mmHg. Moreover, there were occasional discrepancies of sufficient magnitude and duration which may limit the clinical usefulness of the N-CAT in patients in whom continuous and accurate blood pressure measurement is required.RésuméLe N-CAT est un nouveau moniteur de pression artérielle qui utilise le principe de tonométrie artérielle (TBP) pouvant déterminer la pression systolique, diastolique et moyenne de façon continue et non invasive. Le but de cette étude était d’évaluer la précision et la fiabilité de la TBP par rapport à la pression artérielle invasive (IBP) chez des patients après une chirurgie cardiaque, hémodynamiquement stable mais manifestant une fibrillation auriculaire rapide (FC > 100 batt/min). Il y avait une différence significative entre la pression systolique (−1.7 mmHg) et diastolique (+0.9 mmHg) derivées par la TBP visà-vis IBP sans qu’il y ait de différence pour la pression moyenne entre les deux méthodes. Le N-CAT s’est avéré fiable dans sa capacité de suivre les changements de pression artérielle. Ses biais TBP sysolique, diastolique et moyen sont −1,71 ± 4,6, 0,99 ± 4,6 et 0,33 ± 4,2 mmHg respectivement. Ces valeurs de biais répondent aux critères d’équivalence pour une pression invasive. Malgré cela, approximativement 20% des valeurs de TBP étaient > ±10 mmHg tandis que 5% étaient > ±20 mmHg. De plus, il y eut des moments où la différence entre la TBP et la IBP était d’une durée et de magnitude non acceptable, limitant son utilité clinique chez des patients où la mesure de la pression artérielle, de façon exacte et continue, est souhaitable.

Sedation in Critically Ill Patients

Provision of anxiolysis and analgesia in critically ill patients is mandatory to improve patient comfort without undue autonomic or haemodynamic adverse effects. The assessment of the level of sedation in the intensive care unit (ICU) by means of scoring systems is important because both undersedation and over-sedation can be counterproductive. Scoring systems, such as the Ramsay Sedation Score or the Modified Observer’s Assessment of Alertness/Sedation Scale, offer an accurate means of communicating clinical information and monitoring clinical progress.Understanding how the pharmacokinetic and pharmacodynamic profiles of sedative and analgesic agents are altered in critically ill patients is essential for administering effective care. Midazolam and lorazepam are commonly used to provide anxiolysis and amnesia. Although there are variations in morphine metabolism and/or excretion in certain disease states, it remains the opioid of choice for critically ill patients. Because of its unique pharmacokinetic properties, remifentanil may eventually prove to be an interesting alternative. Propofol possesses many characteristics of the ideal sedative agent: rapid onset of effect, easy titration, unaltered pharmacokinetics in hepatic and renal dysfunction, and rapid recovery after prolonged infusion.Conditions most likely encountered in the ICU are reviewed and practical recommendations are provided. Sedation in patients with multiple organ failure raises several interesting problems regarding distribution volumes, plasma protein binding, metabolic rate, tissue perfusion, drug excretion and requirement for prolonged sedation. Weaning from prolonged sedation can be difficult and may reveal drug dependency. The use of propofol can ease the transition from long term benzodiazepine use.Patients with respiratory failure are a special group in whom propofol seems to have a favourable profile. Unless absolutely necessary, neuromuscular blocking agents should be avoided. If these agents must be used, it is incumbent to provide appropriate sedation and monitor the neuromuscular junction with a peripheral nerve stimulator. Opioid drugs should be used sparingly.Compared with other medical conditions, sedation post-cardiac surgery has received a lot of attention. Propofol or midazolam in association with morphine are effective and well tolerated. Both can be use for short term sedation without jeopardising early tracheal extubation.

Can l-arginine improve myocardial protection during cardioplegic arrest? Results of a phase I pilot study

BACKGROUND L-arginine appears to improve myocardial protection during cardioplegic arrest in animal models. METHODS To study the clinical effect and safety of L-arginine in humans, a phase I pilot study was performed with 50 patients who underwent coronary artery bypass grafting. We randomly assigned half to a treatment group, which received 1 g of L-arginine administered during the first 30 minutes of cardioplegic arrest induced by either warm or cold blood cardioplegia, and half to a control group, which did not receive L-arginine supplementation. RESULTS Age, sex, and preoperative clinical status were similar in both groups. Seventeen patients of each group were administered intermittent warm antegrade blood cardioplegia, whereas the solution needed to be cooled to obtain complete standstill of the remaining eight hearts in each group. An internal thoracic artery graft to the left anterior descending coronary artery was performed in all patients. There was no death and no myocardial infarction in the treatment group, but there were one death and two infarctions in the control group. The amount of serial release of troponin I during the first 72 hours after the operation was similar between the L-arginine group and the control group (p > 0.05). Peak serum troponin levels averaged 4.9 +/- 1.0 microg/L in the arginine group and 3.9 +/- 1.0 microg/L in the control group (p > 0.05). A multivariate analysis of variance showed no effect of L-arginine (p > 0.05) but a significant effect of the temperature of the cardioplegic solution on the release of troponin I (p < 0.05). Serum troponin I levels averaged 2.2 +/- 0.4 microg/L, 4.5 +/- 0.4 microg/L, and 6.9 +/- 0.4 microg/L in the patients with cold cardioplegia and 1.4 +/- 0.3 microg/L, 2.4 +/- 0.3 microg/L, and 3.3 +/- 0.3 microg/L in the patients with warm cardioplegia 1, 2, and 6 hours, respectively, postoperatively. CONCLUSIONS The administration of 1 g of L-arginine during the first 30 minutes of blood cardioplegic arrest did not result in a decrease in the postoperative release of cardiac enzyme; however, cold cardioplegic arrest significantly increased the release of cardiac troponin I postoperatively. There was no significant side effect related to the addition of L-arginine to the cardioplegic solution.

Hemodynamic and pharmacodynamic comparison of doxacurium and high-dose vecuronium during coronary artery bypass surgery: a cost-benefit study

Doxacurium (DOX), a new nondepolarizing neuromuscular blocking drug (NMBD), was compared in a randomized, double-blind fashion to high-dose vecuronium (VEC) in 60 coronary artery bypass grafting (CABG) patients. A third group of 15 patients older than 70 years of age (DOX-70) was added to compare the effects of DOX to VEC in the older population. Endpoints of the study were hemodynamic stability, ease of ventilation and intubation, anesthesiologists satisfaction, drug interventions to correct hemodynamic instability, and total cost of the drug. Anesthesia was induced with fentanyl (30 micrograms/kg) along with the NMBD (DOX 80 micrograms/kg, VEC 400 micrograms/kg) over a 2-minute period. Following induction, heart rate (HR) and mean arterial pressure (MAP) were decreased (P < 0.01) in all groups. Tracheal intubation caused the HR to return to baseline in the DOX-70 group. There was no difference in central venous pressure, pulmonary artery occlusive pressure, cardiac index, systemic vascular resistance, and drug intervention for DOX and VEC. None of the patients had evidence of myocardial ischemia. There was a statistically significant but clinically irrelevant decrease in central venous pressure and systemic vascular resistance in the DOX-70 group. The durations of the induction and maintenance doses of DOX were similar in the younger and older patients. Although the intubating dose of VEC had a faster onset of action, this had no effect on the ease of ventilation, conditions for tracheal intubation, and overall anesthesiologist satisfaction. The total cost for each NMBD was not different.(ABSTRACT TRUNCATED AT 250 WORDS)