Robert J. Hudson

Pharmacokinetics of Sufentanil in Patients Undergoing Abdominal Aortic Surgery

The authors determined the pharmacokinetics of sufentanil, 12.5 micrograms.kg-1 iv in patients undergoing elective abdominal aortic surgery. The mean age (+/- SD) of the ten patients was 68.4 +/- 7.9 yr; their mean weight was 74.4 +/- 19.1 kg. Six patients underwent aortobifemoral grafting and four had abdominal aortic aneurysm repair. Serum sufentanil concentrations were determined in samples drawn at increasing intervals over a 24-h period. A three-compartment pharmacokinetic model was fit to the concentration versus time data. Total drug clearance was 15.0 +/- 3.2 ml.min-1.kg-1. The volume of distribution at steady-state (Vdss) was 8.7 +/- 4.5 l.kg-1. The elimination half-time were positively correlated with patient age. There were no significant correlations between the pharmacokinetic variables and the duration of aortic cross-clamping, the duration of surgery, or the rate or total volume of iv fluids given intraoperatively. In general surgical patients, the mean elimination half-time of sufentanil has been reported to be 2.7 h. When sufentanil is used in large doses as the primary anesthetic agent for patients undergoing abdominal aortic surgery, the long elimination half-time observed implies that recovery will take much longer than would have been anticipated from previously published pharmacokinetic data.

A Comparison of Desflurane and Isoflurane in Patients Undergoing Coronary Artery Surgery

Animal studies indicate that desflurane and isoflurane have similar hemodynamic effects when administered in equipotent anesthetic concentrations. The authors compared desflurane and isoflurane, used as primary anesthetics for patients undergoing elective coronary artery bypass surgery whose left ventricular ejection fractions were greater than 0.34. After induction of anesthesia with thiopental (dose 180 +/- 45 mg [mean +/- standard deviation]) and fentanyl, 10 micrograms.kg-1, either desflurane or isoflurane was administered to maintain systolic blood pressure within 70-120% of, and heart rates less than 120% of, the patients average preoperative values. If adjusting the end-tidal anesthetic concentration within the range of 0-2.0 MAC could not maintain these predefined hemodynamic limits, additional fentanyl or vasoactive drugs were used. Induction and maintenance of anesthesia was accompanied by a significant decrease in mean arterial pressure in both groups (desflurane 97 +/- 12 mmHg at control, decreasing to 71 +/- 5 mmHg during skin preparation; isoflurane 95 +/- 9 mmHg at control, 74 +/- 9 mmHg during skin preparation). One minute after sternotomy, mean arterial pressure in the isoflurane group had returned to control, 97 +/- 9 mmHg, which was significantly greater than in the desflurane group, 87 +/- 12 mmHg. Systolic arterial pressure was also significantly greater in the isoflurane group 1 min after intubation, during skin preparation, and 1 min after sternotomy. Otherwise, the hemodynamic effects of these volatile agents were similar. There were no differences between groups in the incidence of ECG changes indicative of myocardial ischemia prior to cardiopulmonary bypass, perioperative myocardial infarction, or perioperative mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of clonidine with conventional preanesthetic medication in patients undergoing coronary artery bypass grafting

In this controlled study, we compared clonidine with conventional premedication in 35 patients undergoing coronary artery bypass grafting (CABG).After premedication with clonidine 5 [micro sign]g/kg PO (Group C, n = 11), lorazepam 60 [micro sign]g/kg PO (Group L, n = 13), or morphine 0.1 mg/kg plus scopolamine 6 [micro sign]g/kg IM (Group M, n = 11), sedation, anxiety, and quality of premedication were graded. After the administration of sufentanil 2.0 [micro sign]g/kg over 12.5 min, a computer-assisted infusion device targeted a sufentanil effect-site concentration of 0.75 ng/mL. Hemodynamic variables, end-tidal isoflurane concentration (ET-ISO), the electroencephalographic spectral edge, and the serum sufentanil concentration (SUF) were measured. There were no intergroup differences in anxiety, sedation, quality of premedication, the dose of sufentanil causing unconsciousness, or the electroencephalographic (EEG) response to induction. Intraoperative SUF was stable, with no intergroup difference. The average prebypass ET-ISO was lower in Group C than in Group M. The ET-ISO and peak ET-ISO after intense surgical stimulation were lower in Group C versus Groups L and M. Mean arterial blood pressure was lower in Group C versus Groups L and M. There were no intergroup differences in pharmacologic intervention, time to extubation, or intensive care unit stay. Clonidine produces sedation, anxiolysis, and quality of premedication comparable to conventional premedication. Compared with other drugs, clonidine does not alter the dose of sufentanil inducing unconsciousness or EEG slowing, but it uniquely reduces isoflurane requirements. Implications: In patients undergoing coronary artery bypass grafting, clonidine produces sedation and relieves anxiety as effectively as conventional premedication. Clonidine does not uniquely alter the dose of sufentanil inducing unconsciousness or electroencephalographic slowing, but it significantly reduces isoflurane requirements. (Anesth Analg 1998;87:292-9)

Concentration-response relationships for fentanyl and sufentanil in patients undergoing coronary artery bypass grafting

Background Concentration‐response relationships for sufentanil and fentanly are undefined in patients undergoing coronary artery bypass grafting. Methods Separate studies of sufentanil and fentanyl were performed in lorazepam‐premedicated patients undergoing coronary artery bypass grafting. Patients were assigned randomly to groups with different prebypass effect‐site opioid concentrations targeted by computer‐assisted infusion. The target sufentanil concentrations were 0.4 ng/ml (group LS, n = 11), 0.8 ng/ml (group MS, n = 10), and 1.2 ng/ml (group HS, n = 11); the target fentanyl concentrations were 5 ng/ml (group LF, n = 7), 10 ng/ml (group MF, n = 7), and 15 ng/ml (group HF, n = 6). Propofol at a dose of 1 mg/kg was administered at induction of anesthesia and isoflurane was used for hemodynamic control. Hemodynamics, end‐tidal isoflurane concentration, and opioid concentration in arterial blood were measured at specific intervals. Results Intraoperative opioid concentrations were constant, averaging 0.71 +/− 0.13, 1.25 +/− 0.21, and 2.03 +/− 0.46 ng/ml for groups LS, M (S), and HS, respectively, and 7.3 +/− 1.1, 13.2 +/− 2.2, and 24.4 +/− 5.8 ng/ml for groups LF, MF, and HF, respectively (all mean +/− SD). Isoflurane requirements were significantly greater in group LS than in groups MS and HS and greater in group LF than in groups MF and HF. The serum opioid and end‐tidal isoflurane concentrations were correlated significantly. There were no intergroup differences in hemodynamics. Conclusions Serum sufentanil and fentanyl concentrations of 0.71 +/− 0.13 ng/ml and 7.3 +/− 1.3 ng/ml, respectively, are on the steep parts of the concentration‐response relationships and facilitate prebypass hemodynamic control in patients undergoing coronary artery bypass grafting with opioid‐isoflurane anesthesia. Concentrations of sufentanil >or= to 1.25 +/− 0.21 ng/ml and of fentanyl >or= to 13.3 +/− 2.2 ng/ml minimize isoflurane requirements but do not improve hemodynamic control.

Drug Interactions with Sufentanil Hemodynamic Effects of Premedication and Muscle Relaxants

Induction of anesthesia with synthetic opioids is occasionally accompanied by undesirable hemodynamic changes such as tachycardia and hypertension, or bradycardia and hypotension. We hypothesized that drug interactions cause many of these adverse responses. Therefore, we conducted a randomized double-blind study to investigate the interactive effect of premedication and muscle relaxants on the hemodynamic response to induction with intravenous (iv) sufentanil 10 micrograms.kg-1. Eighty patients with left ventricular ejection fraction greater than or equal to 0.40, undergoing elective coronary artery surgery, were premedicated with either morphine 0.1 mg.kg-1 and scopolamine 6 micrograms.kg-1 intramuscularly, or lorazepam 60 micrograms.kg-1 orally, and paralyzed with either pancuronium 0.1 mg.kg-1 or vecuronium 0.1 mg.kg-1 iv. The four treatment groups were SP (morphine-scopolamine + pancuronium), LP (lorazepam + pancuronium), SV (morphine-scopolamine + vecuronium), and LV (lorazepam + vecuronium). Hemodynamics were recorded at three time periods: 1) control, 2) induction, and 3) intubation. Premedication-relaxant interactions significantly affected hemodynamics. In group SP, mean heart rate (HR) increased significantly on induction (56 +/- 11 to 69 +/- 13 beats.min-1), while mean arterial pressure (MAP) and cardiac index (CI) were unchanged. HR, MAP, and CI were significantly higher after induction in group SP compared to the other three groups. In group LP, mean HR increased less than in group SP (56 +/- 8 to 62 +/- 14 beats.min-1), whereas MAP and CI declined significantly. In group SV, HR and CI were unchanged, but MAP declined significantly. In group LV, HR was stable, whereas both MAP and CI declined significantly. The incidence of pharmacologic interventions during the study period also differed significantly among groups.(ABSTRACT TRUNCATED AT 250 WORDS)

High-dose thiopentone for open-chamber cardiac surgery: a retrospective review.

PurposeHigh-dose thiopentone has been reported to reduce the incidence of neurological dysfunction after open-chamber cardiac surgery. However, this technique delays trachéal extubation and increases requirements for inotropic support after cardiopulmonary bypass. As a quality assurance measure to determine the safety of high-dose thiopentone, we reviewed the records of all patients undergoing elective, open-chamber surgery at our institution between 1st March, 1987 and 31st Dec, 1989.MethodsThe charts of 236 patients were reviewed retrospectively, and 227 met our inclusion criteria. The perioperative characteristics of patients anaesthetized with thiopentone (Group T, n = 80) were compared with those of patients anaesthetized with opioids (Group O, n = 147).ResultsAnaesthetic technique was chosen by the attending anaesthetist. In Group T (n = 80) thiopentone 38.1 ± 11.8 mg· kg−1 was infused to produce electroencephalographic burst-suppression during bypass. Moderate hypothermia and arterial line filtration were used during bypass. The groups did not differ with respect to demographics, type of surgery, or conduct of bypass. There were no strokes in Group T and 4 in Group O (P = NS). The time to extubation was prolonged in Group T compared with Group O(39 ±51 vs 27 ± 24 h, P = 0.014), as was the duration of slay in intensive care (66 ± 56 vs 51 ± 29 h, P = 0.010). Thiopentone did not increase the need for inotropic or mechanical support after bypass, ln-hospital mortality was lower in Group T than in Group O (1.2% vs 9.5%, P= 0.034).ConclusionsHigh-dose thiopentone delays extubation after open-chamber procedures. However, the technique appears safe, and further prospective investigation is justifiable.RésuméObjectifOn a rapporté que les doses élevés de thiopentone diminuaient l’incidence de la dysfonction neurologique après la chirurgie à coeur ouvert. Cependant, cette méthode retarde l’extubation de la trachée et augmente le besoin de soutien inotrope après la circulation extracorporelle. Comme mesure d’assurance-qualité effectuée pour déterminer la sécurité du thiopentone à haute dose, nous avons révisé les dossiers de tous les patients de notre institution opérés pour une chirurgie à coeur ouvert entre le premier mars 1987 et le 31 décembre 1989.MéthodesLes dossiers de 236 patients ont été révisés rétrospectivement et 227 ont rencontré nos critères d’admissibilité. Les caractéristiques périopératoires des patients anesthésiés au thiopentone (groupe T, n = 80) ont été comparées à celles des patients anesthésiés aux morphiniques (groupe O, n = 147).RésultatsLa technique anesthésique était choisie par l’anesthésiste responsable. Dans le groupe T, le thiopentone 38,1 ± 11.8 mg· kg−1 était perfusé de façon à produire un burst suppression électroencéphalographique pendant la circulation extracorporelle (CEC). Aucun accident cérébrovasculaire n’est survenu dans le groupe T mais il y en a eu quatre dans le groupe O. L’intubation a été. prolongée dans le groupe T comparativement au groupe O (39 ± 51 vs 27 ± 24 h, P = 0,014) de même que la durée du séjour à l’unité des soins intensifs. Le thiopentone n’a pas augmenté le besoin de support inotrope ou mécanique après la CEC. La mortalité intrahospitalière était plus basse dans le groupe T que dans le groupe O (1,2% vs 9,5%, P = 0,034).ConclusionsLes doses élevées de thiopentone retardent l’extubation après les interventions à coeur ouvert. Cependant, la technique semble sùre, ce qui justifie des recherches ultérieures.

Continuous opioid infusions for neurosurgical procedures: a double-blind comparison of alfentanil and fentanyl

The ability of continuous infusions of opioids to control hypertension at the end of neurosurgical procedures without compromising prompt emergence was studied in patients undergoing craniotomy for supratentorial tumours. Four infusion regimens were compared in a randomized double-blind fashion; three of alfentanil and one of fentanyl. Low-dose alfentanil was administered to nine patients (35.1 μg · kg−1 then a continuous infusion of 16.2 μg · kg−1 · hr−1); mid -dose alfentanil to eight patients (70.2 μg · kg−1 then 32.4 μg · kg−1 · hr−1); high-dose alfentanil to eight patients (105.3 μg · kg−1 then 48.6 μg · kg−1 · hr−1). Eight additional patients were given fentanyl (8.3 μg · kg−1 then 1.6 μg · kg−1 · hr−1). Using published values for the pharmacokinetic variables of alfentanil and fentanyl, modelling predicted stable concentrations of 60, 120, l80 ng · ml−1 for the alfentanil infusion regimens respectively and 2 ng · ml−1 with the fentanyl regimen. Maintenance anaesthesia comprised the opioid infusion, 50% N2O in O2 and isoflurane titrated to control mean arterial pressure (MAP) within 20% of ward MAP. Isoflurane was discontinued after closure of the dura. Nitrous oxide was discontinued at the same time as reversal of neuromuscular blockade. The opioid infusion was discontinued with closure of the galea. A greater time-averaged isoflurane concentration was required to control MAP within the prescribed limits in the low alfentanil group (ANOVA; P < 0.05). The PaCO2 at two, five and 30 min after extubation were not different among groups. The times from discontinuing N2O to eye opening and tracheal extubation were not different. The time to follow commands was longer in the low alfentanil group (P < 0.05). Vasodilator therapy (to control MAP < 120% of ward MAP) with either labetalol or diazoxide was required less often in the high alfentanil group (318 patients; 38%) versus 100% in the low alfentanil groups (P < 0.05). Prompt emergence with the higher doses of opioids suggests that the volatile agent sparing effect of opioids can be used to advantage in these procedures.RésuméLes effets de la perfusion continue d’ opiacés sans compromettre le réveil rapide sur le contrôle de l’hypertension après les procédures neurochirurgicales furent étudiés chez des patients subissant une craniotomie pour des tumeurs cérébrates. Quatre régimes de perfusion furent comparés d’une façon randomisée à double insu, trois d’alfentanil et une de fentanyl. Des doses faibles d’alfentanil furent administrées chez neuf patients (35,1 μg · kg−1 suivies d’une perfusion continue de 16,2 μg · kg−1 · hr−1); des doses moyennes d’alfentanil pour huit patients (70,2 μg · kg−1 suivi 32,4 μg · kg−1 · hre−1); des doses élevées d’alfentanil pour huit patients (105,3 μg · kg−1 suivi 48,6 μg · kg−1 · hre−1. On a donné du fentanyl chez huit patients additionnels (8,3 μg · kg−1 suivi de 1,6 μg · kg−1 · hre−1). Utilisant les valeurs publiées sur les variables pharmacocinétiques de l’alfentanil et du fentanyl, des concentrations stables furent prédites pour 60, 120, 180 ng · ml−1 pour les perfusions d’alfentanil respectivement et pour 2 ng · ml−1 pour le régime au fentanyl. Le maintien de l’anesthésie a compris la perfusion d’opiacés, 50% N2O et oxygène avec l’isoflurane titré afin de contrôler la pression artérielle moyenne (MAP) à l’intérieur de 20% des valeurs obtenues sur les étages. L’isoflurane fut cessé après fermeture de la dure-mère. Le protoxide dazote fut cessé en même temps qu’on a antagonisé le blocage neuromusculaire. La perfusion d’opiacé fut discontinué à la fermeture de l’aponévrose. Une plus grande concentration d’isoflurane fut requise afin de controler le MAP à l’intérieur des limites prescrites par le groupe a dose faible d’alfentanil (ANO VA:P < 0,05). La PaCO2 à deux, cinq et trente minutes après extubation n’était pas différente entre les groupes. Les temps à partiir de la cessation de protoxyde d’azote jusqu’ à l’ouverture des yeux et l’extubation n’ étaient pas différents entre les groupes. Les temps de réponse aux ordres étaient plus longs dans le groupe à dose faible d’alfentanil (P < 0,05). La thérapie aux vasodilatateurs (afin de contrôler une MAP < 120% des valeurs sur l’étage) avec soit du labétalaol ou diazoxide était moins fréquemment requise dans le groupe alfentanil à haute dose (3/8 des patients; 38%) versus 100% dans le groupe à basse dose d’alfentanil (P < 0,05). Le réveil rapide avec les hautes doses d’opiacés suggèrent que l’effet d’économie des opiaces par l’agent volatil peut être utilisé avec avantage dans ces procédures.

ALFATHESIN AND ENFLURANE: SYNERGISTIC CENTRAL NERVOUS SYSTEM EXCITATION?

This case report describes signs of central nervous system excitation occurring after administration of alfathesin and enflurane in doses lower than those previously associated with this type of phenomena (alfathesin 36 microlitres/kilogram, enflurane two volumes per cent). This suggests that these drugs may interact to increase the probability of seizure-like activity.RésuméDans cette observation, les auteurs font la description des symptômes d’excitation du système nerveux central survenus après l’administration d’alfatésine et d’enflurane à des doses inférieures à celles qu’on associait jusque là à ce genre d’incident. Us expriment l’opinion qu’il pourrait y avoir une interaction entre ces deux medicaments qui aurait pour effet d’augmenter l’incidence des crises convulsivés.