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Background: Obesity changes body composition including fat free mass (FFM), regarded as the “pharmacologically active mass”. Scaling drug doses to obese patients by total body mass (TBM) results in overdose. We aimed to determine the success rate of inducing anaesthesia in normal, overweight and obese patients with propofol, using an adjusted body mass scalar (ABM), which embodies the increased FFM of obese patients.Methods: Ninety-six patients were divided into three groups according to body mass index (BMI): normal, overweight and obese. Propofol 2 mg/kg ABM was administered according to the equation: ABM = IBM + 0.4(TBM – IBM), where IBM = ideal body mass. Induction success was assessed clinically and by electroencephalographic spectral entropy.Results: The groups were similar regarding gender, age, height and IBM. One patient was morbidly obese (BMI = 44). State entropy (SE) decreased to < 60 in 33/33, 28/29 and 33/34 patients in the normal-weight, overweight and obese groups respectively, an overall success rate of 97.5% (95% confidence interval 92.7% to 99.4%). Median lowest achieved SE values and median times that SE remained < 60 did not differ between groups, however the individual values ranged widely in all three groups. Induction failed in the two patients whose SE did not decrease to < 60 (one overweight and one obese).Conclusions: The ABM-based propofol induction dose has a high success rate in normal, overweight and obese patients. Further studies are required to determine the feasibility among morbidly obese patients.Keywords: administration and dosage, body mass index, body compositions, propofol

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Background: A 26-year-old, 59 kg female was administered morphine 10 mg during tonsillectomy, and 5 mg in the recovery room. She died 5 hours after the operation. Hypoxic cerebral injury, arising from morphine side-effects, was pronounced the cause of death, in spite of morphine being undetectable in blood. Recent pharmacokinetic-pharmacodynamic modelling indicates that, after a single intravenous dose, maximum respiratory depression occurs after 1 hour and 40 minutes and persists for hours. Furthermore, respiratory depression is accompanied by airway obstruction, sleep potentiates respiratory depression and airway obstruction, pain stimulates breathing and antagonises respiratory depression, pain relief unmasks respiratory depression, and a slow breathing rate is uncommon.Methods: Pharmacokinetic-pharmacodynamic simulations were used to estimate the time course of morphine effect-site concentrations in an “average” 59 kg female, and to calculate the degree of resulting respiratory depression.Results: Morphine effect-site concentrations approached dangerous levels for respiratory depression andpersisted for hours, while plasma concentrations were undectectably low. Discussion: Court testimony indicates that additional factors contributed to the patient’s demise. Respiratory depression was potentiated by pain relief following quinsy tonsillectomy, and by falling asleep. The airway wasobstructed, as witnessed both by nurses and a fellow patient. In addition, nursing staff failed to recognise that snoring can indicate a dangerously obstructed airway.Conclusions: Dangerous respiratory depression often goes unrecognised in surgical wards. Strategies for improved safety include education of nursing and other staff regarding the following aspects of respiratorydepression: (i) recognition of delayed and prolonged respiratory depression; (ii) noisy breathing indicatesobstructed breathing; (iii) respiratory rate is an unreliable monitor of respiratory depression; (iv) training in airway management should be compulsory; (v) sleeping patients should be administered oxygen, and pulse oximetry monitoring should be done (especially at night); (vi) more local anaesthesia should be administered for postoperative pain; (vii) combination analgesic therapy (NSAIDs, paracetamol, ketamine, dexmedetomidine, gabapentin) should be utilised to reduce morphine requirements; (viii) high risk patients (e.g. elderly, obese, sleep-apnoea syndrome) should be identified; (ix) sedation scores should be recorded to detect obtunded patients. Morphine plasma concentrations do not reflect pharmacological activity. Keywords: morphine; adverse effects; respiratory insufficiency; pharmacokinetics; pharmacodynamics

Background: Investigators have reported inter-patient variability with regard to propofol dosage for induction of anesthesia, since early dose finding studies. With the arrival of generic formulations of propofol, questions have arisen regarding further variability in dose requirements. Various studies have confirmed that generic propofol preparations are pharmacokinetically and pharmacodynamically equivalent to Diprivan®. Nevertheless a number of practitioners are under the impression that certain generic propofol preparations require greater doses for induction of anaesthesia than does Diprivan®.Methods: 20 female patients of ASA status I-II, between the ages of 18-55 years, scheduled for routine surgery were randomly allocated to two groups to undergo induction of anaesthesia using two different propofol formulations; Diprivan® and Propofol 1% Fresenius®. Either preparation was administered using a target-controlled infusion of propofol (STEL-TCI) targeting the plasma (central) compartment at a concentration of 6 μg.ml-1, employing the pharmacokinetic parameters of Marsh et al. A processed EEG (bispectral index) was continuously recorded. Loss of consciousness (LOC) was regarded as the moment at which the patient could not keep her eyes open and was confirmed by the absence of an eyelash reflex. At this point propofol administration was discontinued and data were recorded for a further two minutes, before administering an appropriate opioid and/or nitrous oxide/volatile agent and/or muscle relaxant to maintain anaesthesia. Time to LOC after start of propofol administration, and the dose of propofol administered during induction were annotated. Results: There were no demographic differences between the groups. There were no differences between the groups with regard to the mean dose for LOC, time to LOC and to the mean BIS values obtained at the following stages: awake, at LOC, at 1 and 2 minutes after LOC as well as the lowest recorded value.Conclusions: Our results confirm that the two propofol formulations that we studied, are pharmacologically equivalent with regard to induction of anaesthesia. Other mechanisms can explain the variability in clinical response to bolus administration of propofol. The most important is the recirculatory or “front-end” kinetics of propofol in which cardiac output plays a major role, as well as the rate of drug administration. Emulsion degradation can also influence dose-response and in this regard it should be noted that the addition of foreign substances such as lignocaine, can result in rapid deterioration of the soyabean emulsion.

Objectives: Comparison of hemodynamics, circulatory efficiency, myocardial ischemia and recall during and after sevoflurane or halothane (0.6 MAC {Minimum Alveolar Concentration} inspired) combined with a target-controlled sufentanil infusion (2 ng.ml-1) for coronary artery bypass grafting. Methods: Prospective randomised non-blinded study in a university teaching hospital of 45 patients undergoing on-pump surgery. Inhalation anesthetic agent was delivered before, during and after cardiopulmonary bypass. Results: Intraoperative hemodynamics were maintained within predetermined limits using vasoactive and cardioactive drugs. Heart rate was unchanged from baseline, however the sevoflurane-sufentanil group required more glycopyrrollate, indicating a tendency towards a slower heart rate. In both groups, similar low incidences of myocardial ischemia were detected. After induction of anesthesia, as well as intraoperatively, oxygen consumption decreased by up to 36.6% compared with the awake values in both groups. Oxygen delivery remained unchanged during all measuring periods. Mixed venous oxygen tensions rose after induction, even in patients with cardiac indices below 2.2 L.min-1.m-2, indicating maintenance of an effective circulation when utilising these techniques. Twelve hours postoperatively, oxygen consumption exceeded awake values by 31%. No explicit recall was reported by any patient on enquiry on the third postoperative day. Conclusions: Low concentrations of sevoflurane or halothane, supplementing target-controlled sufentanil infusions, were both suitable for providing anesthesia for coronary bypass surgery.Keywords: Coronary artery bypass grafting, anesthesia, hemodynamics, sevoflurane, halothane, sufentanil, mixed venous oxygen tension, oxygen consumption, balanced anesthesia