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Introduction: The first commercially available target-controlled infusion pump, the “Diprifusor”, employed a “Marsh” pharmacokinetic-pharmacodynamic parameter set, and this model (the Diprifusor-Marsh model) is also available in several of today’s pumps. However, it is unsuited for effect-site, target-controlled infusions (Ce-TCI) because it assumes slow transfer between blood and the effect-site (ke0 = 0.26 min-1). We hypothesised that a faster ke0 of 1.21 min-1 (Adjusted-Marsh model) for Ce-TCI would result in hypnotic effects equivalent to that of the Schnider parameter set (Schnider model). Methods: We replicated a previously published study that demonstrated the Diprifusor-Marsh model’s unsuitability for Ce-TCI. We randomised 40 unpremedicated young adults into two groups to receive Ce-TCI, employing either the Schnider model or the Adjusted-Marsh model. We infused propofol at 3 000 mg.hour-1, while running a pharmacokinetic simulation and recording the electroencephalographic bispectral index (BIS) electronically. At loss of consciousness (LOC), indicated by a syringe-drop, we converted the infusion to Ce-TCI, targeting the effect-site concentration (Ce) observed at LOC, for 20 minutes. We regarded a difference of 10 BIS-units as clinically important. Results: There were no statistically significant differences between the group medians regarding time-to-LOC, induction-dose, BIS at LOC and Ce-target. BIS decreased monotonically in both groups from a median of 78.5 at LOC to a steady-state median (25–27) at 15 minutes. The BIS of the Adjusted-Marsh model group closely followed the BIS of the Schnider model group. At steady state, the median BIS difference (95% CI) was -0.3 (-5.7 to 5.3), which was within the predefined interval for declaring equivalence. The Schnider model group’s mean BIS at steady state did not differ from that of the previous study’s Schnider model group. Conclusion: Reasons for the progressive BIS decrease to lower than expected values include delayed response-times by the BIS monitor, Ce overshoot explained by front-end kinetics, neural inertia and the choice of surrogate LOC indicator. We conclude that Ce-TCI using the Adjusted-Marsh parameter set results in equivalent hypnotic effects to those of the Schnider model, with the proviso that this may apply only to young adults of normal body habitus.

Background: Burnout is a psychological syndrome that develops in response to chronic job-related stressors. Its three predominant manifestations are emotional exhaustion, cynicism, and feelings of ineffectiveness and unfulfillment (low efficacy). Our study objectives were to establish the prevalence and severity of burnout among South African anaesthetists and to compare the results with previous studies. We also identified areas of work-life that predispose to burnout and we report these results in a separate paper (Part 2).1Methods: We e-mailed invitations to 1 852 SASA members, requesting responses to two validated questionnaires, the Maslach Burnout Inventory and the Areas of Worklife Scale. We categorised respondents according to the “Emotional Exhaustion+1” principle, whereby a person is regarded as being clinically burned-out if he/she has a a high score for emotional exhaustion, plus either a high cynicism score or a low efficacy score. High scores for all three dimensions defined “extreme burnout”.Results: 189 public sector and 309 private sector anaesthetists responded. 85% of public sector respondents worked in academic hospitals. Compared to those in private practice, public sector anaesthetists exhibited a greater prevalence and severity of burnout. This was manifested by: (1) more adverse scores for all three burnout dimensions; (2) a greater prevalence of clinically diagnosable burnout (36.5% vs. 14.2%) as well as “extreme burnout” (17.5% vs. 6.5%). Public sector anaesthetists experienced more burnout than in other countries.Conclusions: The prevalence of burnout is unacceptably high among South African anaesthesia providers, particularly in public hospitals. This poses an immediate threat to both anaesthetists’ mental and physical health and to patient safety. The severity and prevalence in teaching institutions jeopardises the current effectiveness and future sustainability of the South African healthcare system.

Introduction: The purpose of this two-part study was to determine the prevalence and severity of the burnout syndrome among South African anaesthetists working in the public and private sectors, and to identify areas of work-life (AWLs) that predispose to burnout. We reported our burnout findings in Part 1.1 In this paper (Part 2) we report on the AWLs.Methods: Invitations were e-mailed to 1 852 SASA members, requesting responses to a validated questionnaire, the Areas of Worklife Survey (Mindgarden Inc. Menlo Park, USA). The questionnaire results in scores for six AWLs that impact on the development of the burnout syndrome, namely workload, control, reward, community, fairness and values.Results: 189 public sector and 309 private sector anaesthetists responded. 85% of public sector respondents worked in academic hospitals. The values AWL could not be properly assessed due to respondents’ misinterpretations regarding that particular item. Compared to private sector, public sector anaesthetists had lower (i.e. more adverse) median scores for five AWLs. Greater proportions of public sector anaesthetists had low scores for the five AWLs. Correspondingly, smaller proportions of public sector anaesthetists had high (i.e. favourable) scores for workload, control, reward, and fairness. Multivariable least squares regression analysis identified the following significant explanatory variables for the following burnout dimensions: For emotional exhaustion these were workload, reward, community and control. For cynicism they were workload,reward, control, gender and years of experience. Predictors for efficacy were reward, community, control and years of experience. Logistic regression analysis included workload, reward and control AWL as explanatory variables for a clinical diagnosis of burnout with workload the dominant variable.Conclusions: Public sector anaesthetists experience more adverse AWLs than those in private practice. The most important factor appears to be excessive workload. Additionally, the reward, community and control AWLs are important determinants of anaesthetists’ psychological relationships with their work.

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...

Background: In obesity, accurate perioperative blood pressure measurement using upper arm, non-invasive blood pressure (NIBP) is technically challenging. Proximal forearm NIBP may be an acceptable substitute. Mean arterial blood pressures (MAP) estimated by proximal forearm NIBP were compared with direct intra-arterial measurements. It was hypothesised that the measurement techniques would be interchangeable if between-technique MAP differed ≤ 20% and MAP ratios were < 1.2and > 0.8.Method: A total of 30 adults with body mass index ≥ 30 kg/m2 in whom perioperative intra-arterial blood pressure measurement was considered mandatory were enrolled. MAP measurements using the two techniques were obtained at three random intervals in each patient. Bland–Altman analyses were employed.Results: Forearm mean NIBP MAP overestimated mean intra-arterial MAP by 2.2 (SD 8.1; range from 23.8 to –19.4 mmHg; p = 0.011, 95% CI 3.9 to 0.5). However, Bland–Altman analyses revealed a wide dispersion with several MAP differences and MAP ratios exceeding the pre-specified bounds for interchangeability.Conclusion: Forearm NIBP could not be considered interchangeable with direct intra-arterial MAP measurements in obese patients.Keywords: Blood pressure monitoring, comparative study, forearm, intra-arterial, obese

Background: Propofol lipid emulsion supports bacterial growth and various outbreaks of postoperative infection are attributed to extrinsic contamination. This study’s objectives were to ascertain propofol administration practices among South African anaesthesiologists and to determine the influence of the 2014 South African Society of Anaesthesiologists (SASA) Guidelines for Infection Control in Anaesthesia.Methods: A total of 1 598 SASA members were invited to participate anonymously and 634 replies were received. Using a riskscoring system developed from 13 questionnaire items, 542 respondents who administer propofol infusions were stratified into Low-, Moderate-, High- and Very High-Risk groups.Results: The majority (65%) of the 542 participants who administer propofol infusions were classified as Moderate Risk, 29% as Low Risk and 6% as High and Very High Risk. Some 61% were aware of the SASA Guidelines, of whom 47.3% had studied them. The median risk-score of the Studied Guidelines group was significantly smaller (p < 0.001). They included a greater proportion who were categorised as low risk (58% vs. 45%) and a lower proportion who were moderate risk (38% vs. 51%). Proportions of high-risk individuals did not differ. Of the total 634 respondents, 247 used rubber-stoppered vials of whom 28% had studied the SASA Guidelines; 20% of the Studied Guidelines group often/always shared vial contents between patients versus 12% of those who had not studied them (p = 0.13). Conversely, 40% (studied group) versus 13.6% (not-studied group) often/always wiped the diaphragm and seldom/never shared vial contents between patients (p < 0.0001). In all, 25% of the total 634 respondents often/ always pre-prepared multiple propofol syringes; 5.0% diluted propofol and often/always pre-prepared syringes.Conclusion: Penetration of the SASA Guidelines was low. Differences in unsafe practices among anaesthesiologists who had read the guidelines were statistically significant but clinically inconsequential. This highlights a need for greater publicity, emphasising their practical importance.Keywords: drug compounding, Infection control, propofol, postoperative complications, practice guidelines as topic

It is possible to establish and maintain targeted blood and effect-site drug concentrations with reasonable accuracy using a ‘bolus, elimination, transfer' (BET) infusion regimen. Simulation software that employs pharmacokinetic models can be used to drive infusion pumps or to design manually-controlled BET infusions. Prolonged infusions can result in prolonged recovery times. However the elimination half-lives of infused lipid soluble drugs have little or no relevance to rates of recovery because elimination half-life does not take redistribution from peripheral compartments into account. A better method is to calculate the context-sensitive decrement times (context-sensitive referring to the infusion duration). These are not represented by a single number: they are a continuum of time values that are a function of infusion duration and can be represented by a graph. Considering that decrement times depend on the concentrations achieved as well as the dose history, it is often difficult for clinicians to anticipate a patient's time to recovery. Pharmacokinetic simulation software continuously calculates and displays expected recovery times, helping clinicians to ascertain when to reduce or terminate the infusion.

Uncertainty exists as to the most suitable pharmacokinetic parameter sets for propofol target-controlled infusions (TCI). The pharmacokinetic parameter sets currently employed are clearly not universally applicable, particularly when patient attributes differ from those of the subjects who participated in the original research from which the models were derived. Increasing evidence indicates that the pharmacokinetic parameters of propofol can be scaled allometrically as well as in direct proportion to lean body mass (LBM). Appraisal of hitherto published studies suggests that an allometrically scaled pharmacokinetic parameter set may be applicable to a wide range of patients ranging from children to obese adults. On the other hand, there is evidence that propofol pharmacokinetic parameters, scaled linearly to LBM, provide improved dosing in normal and obese adults. The ‘Schnider’ pharmacokinetic parameter set that has been programmed into commercially available TCI pumps cannot be employed at present for morbidly obese patients (body mass index >40 kg/m2), because of anomalous behaviour of the equation used to calculate LBM, resulting in administration of excessive amounts of propofol. Simulations of TCI using improved equations to calculate LBM indicate that the Schnider model delivers similar amounts of propofol to morbidly obese patients as do the allometrically scaled pharmacokinetic parameter sets. These hypotheses deserve further investigation. To facilitate further investigation, researchers are encouraged to make their data freely available to the WorldSIVA Open TCI Initiative (http://opentci.org).

Background: It has been suggested that spectral entropy of the electroencephalogram as applied in the M-Entropy S/5TM Module (GE Healthcare) does not detect the effects of nitrous oxide (N2O). The aim of this study was to investigate the effect on entropy by graded increases in N2O concentrations in the presence of a constant concentration of sevoflurane, in the absence of surgical stimulation.Method: This single-blind, randomised study was conducted at an altitude of approximately 1 400 m. Patients received sevoflurane 2% (1.7% at sea level) and N2O, at end-tidal concentrations of 0%, 10%, 20%, 30%, 40%, 50%, 60% or 70% (equivalent to 8.5%, 17%, 25.5%, 34%, 42.6%, 51.1% and 59.6% at sea level). Entropy was measured before, during and after N2O administration. The absolute changes and ratios of entropy relative to the baseline were calculated. Between- and within-group comparisons were made using analysis of variance and covariance.Results: None of the entropy variables differed significantly with...

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.Resu...

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.

Background: In 2011, Stellenbosch University introduced a district hospital-based longitudinal integrated model for final-year students as part of its rural clinical school. The present study is an analysis of students’ experiences during the first 3 years of the programme.Methods: All 13 students who started the programme between 2011 and 2013 were interviewed. Thematic networks linking recurrent issues were developed and transcripts were analysed against this framework using ATLAS.ti.Results: Two major themes emerged. These were ‘preparation for being a doctor’ and ‘academic/exam preparation’. Students were overwhelmingly positive about the working atmosphere and their preparation for clinical practice and felt that their learning had been facilitated by the flexibility of the programme and the requirement to take responsibility. This contrasted with their academic (‘book’) learning, which was characterised by uncertainty about expectations, particularly regarding exams and parity with learning at the central teaching hospital. The flexibility of the integrated approach was seen as a problematic lack of structure when it came to academic learning. Negative academic emotions were compounded by some frustration about administrative issues early in the programme.Conclusions: The district hospital-based longitudinal integrated model has great potential as a teaching platform for final-year students; however, students remain concerned about academic learning. Potential strategies to reduce student anxiety include more opportunities for dialogue between rural students and specialist teaching platforms, clearly communicated expectations – both about what the students can expect from the programme and about what is expected from them – and administrative excellence.

Objective To investigate the accuracy of a minimally invasive, 2-step, lookup method for determining mixed venous oxygen saturation compared with conventional techniques. Design Single-center, prospective, nonrandomized, pilot study. Setting Tertiary care hospital, university setting. Participants Thirteen elective cardiac and vascular surgery patients. Interventions All participants received intra-arterial and pulmonary artery catheters. Minimally invasive oxygen consumption and cardiac output were measured using a metabolic module and lithium-calibrated arterial waveform analysis (LiDCO; LiDCO, London), respectively. For the minimally invasive method, Step 1 involved these minimally invasive measurements, and arterial oxygen content was entered into the Fick equation to calculate mixed venous oxygen content. Step 2 used an oxyhemoglobin curve spreadsheet to look up mixed venous oxygen saturation from the calculated mixed venous oxygen content. The conventional “invasive” technique used pulmonary artery intermittent thermodilution cardiac output, direct sampling of mixed venous and arterial blood, and the “reverse-Fick” method of calculating oxygen consumption. Measurements and Main Results LiDCO overestimated thermodilution cardiac output by 26%. Pulmonary artery catheter-derived oxygen consumption underestimated metabolic module measurements by 27%. Mixed venous oxygen saturation differed between techniques; the calculated values underestimated the direct measurements by between 12% to 26.3%, this difference being statistically significant. Conclusion The magnitude of the differences between the minimally invasive and invasive techniques was too great for the former to act as a surrogate of the latter and could adversely affect clinical decision making.

Anaesthesiologists are increasingly more involved in perioperative patient care wherein interpretation of special investigations is crucial to making therapeutic and prognostic decisions. Furthermore, anaesthetic journal publications increasingly rely on diagnostic tests, without paying sufficient attention to the methodology for evaluation of the predictive ability of these tests, particularly when conducting research. The purpose of this article is to provide an introduction to the principles underlying the objective appraisal of diagnostic tests and to provide basic tools for that purpose. Basic concepts about probability and conditional probability are introduced. An explanation is given how Bayes' theorem can be used to apply new information to improve uncertainty about a diagnosis. Various indices of diagnostic accuracy are clarified using simple probabilistic notation applied to a 2x2 table from which they can be calculated. Two clinical examples are employed to illustrate these concepts. The calculations are made easier using a spreadsheet that may be downloaded from the Internet and by using Fagan's nomogram. The use of receiver operating characteristic (ROC) curves for choosing a suitable cut-off point between positive and negative tests is explained.

In this review we intend to ascertain trends in propofol administration for paediatric anaesthesia and sedation.Propofol is being 'discovered' by non-anaesthesiologist practitioners of paediatric sedation. However it appears that the drug is not infrequently administered alone for painful procedures, necessitating large doses that result in uncontrolled general anaesthesia with a high potential for adverse events. An elegant technique comprises small doses of short-acting opioid (e.g. fentanyl 1 mug/kg) with low-dose propofol infusion. This does not result in worsening of pre-existing right-to-left intracardiac shunts. The dilemma is to educate non-anaesthesiologists about propofol pharmacokinetics and pharmacodynamics and in particular about the advantages of combined drug therapy. A paediatric target-controlled system for propofol has undergone preliminary clinical evaluation and it is hoped that administration according to pharmacokinetic principles will refine administration to infants and children. Sporadic cases of the propofol infusion syndrome in patients receiving prolonged sedation in intensive care units continue to be reported (characterized by metabolic acidosis, rhabdomyolysis and myocardial failure). It appears that one mechanism may be a deficiency of mitochondrial oxidative processes possibly induced by a dialyzable substance, perhaps a propofol metabolite. Propofol has been used with some success in treating postoperative laryngospasm and for tracheal intubation without muscle relaxants.Propofol should be used with extreme caution for prolonged sedation in intensive care unit patients, at dose rates of below 5 mg/kg per h, while maintaining extreme vigilance for signs of developing propofol infusion syndrome. If used correctly propofol is a suitable drug for sedation outside the operating room.

Methods Seven academic centres studied 302 patients, using desflurane, enflurane, halothane, or isoflurane using circle-systems and Drager Julian anaesthetic machines, with fresh gas flows ( V ˙ f ) of 3, 1, and 0.5 litre min−1. Volatile agent partial pressures in the breathing system were recorded and agent consumptions measured by weighing. Results At these flows, desflurane consumption depended on V ˙ f . In contrast, halothane consumption was not influenced by V ˙ f . Isoflurane and enflurane showed differences in consumption between flows of 0.5 and 3 litre min−1. Stepwise linear regression suggested that besides V ˙ f , other factors influenced consumption of the more soluble agents (sex, age, weight, height, altitude, and temperature). The partial pressure ratios were independent of V ˙ f for desflurane (end-tidal to fresh gas=0.8), but the ratios of the more soluble agents varied with V ˙ f (end-tidal to fresh gas=0.3–0.7). Conclusions At V ˙ f that involves significant re-breathing, consumption of soluble agents depends only partially on V ˙ f . These results can be explained using Mapleson's hydraulic analogue model.

It has been suggested that the dose requirement for spinal anesthesia (SA) is lower in obese patients for cesarean delivery (CD). In this prospective, observational, noninferiority study, we tested the hypothesis that obesity would not have a clinically important effect on vasopressor requirements or block height.Two groups of 25 parturients, group O (body mass index [BMI]40 kg/m) and group N (BMI32 kg/m) requiring elective CD were recruited. All patients received 10 mg intrathecal hyperbaric bupivacaine coadministered with 10 μg fentanyl. Dermatomal levels were assessed at 5 and 25 minutes after SA, and at completion of surgery, using light touch and cold sensation in response to ethyl chloride. The primary outcomes were phenylephrine requirement in the first 30 minutes after SA, and maximum block height, measured by the sensation of touch and cold. Secondary outcomes were total phenylephrine dose required, changes in hand grip strength, and peak flow rate.There were no significant between-group differences in median block height as assessed by touch at 5 or 25 minutes or by temperature at 5 minutes. At 25 minutes, there was a 2-dermatome difference in median block height for loss of temperature sensation between group O and group N (T2 vs T4, 95% confidence interval [CI] of the difference in medians 0-2 dermatomes). No blocks extended to cervical dermatomes. The median (range) phenylephrine dose for the first 30 minutes was 150 µg (0-900 µg), and 100 µg (0-1250 µg) in group N and group O, respectively. The 95% CI for the difference between the 2 median doses was -150 µg to 100 µg. There were no differences in median percentage reductions in peak flow rate or median hand grip strength after SA. Mean surgical time was longer in group O than in group N (49.1 vs 39.4 min, 95% CI difference 1.7-17.7 min). The mean time for recovery of touch sensation to T10 was longer in group O (152 vs 132 min, 95% CI difference 3.8-36.2 min). No analgesic supplementation was required.Only a minor increase in block height as assessed by temperature occurred in group O at 25 minutes. Vasopressor requirements during the first 30 minutes of SA were equivalent. Time for regression of SA block level was longer in the group O, which may be beneficial considering the longer surgical time. A dose of spinal bupivacaine 10 mg for single-shot SA should not be reduced in morbidly obese parturients.

Background: The theme of the 2014 Southern African Rural Health Conference was ‘Building resilience in facing rural realities’. Retaining health professionals in South Africa is critical for sustainable health services. Only 12% of doctors and 19% of nurses have been retained in the rural areas. The aim of the workshop was to understand from health practitioners why they continued working in their rural settings.Conference workshop: The workshop consisted of 29 doctors, managers, academic family physicians, nurses and clinical associates from Southern Africa, with work experience from three weeks to 13 years, often in deep rural districts. Using the nominal group technique, the following question was explored, ‘What is it that keeps you going to work every day?’ Participants reflected on their work situation and listed and rated the important reasons for continuing to work.Results: Five main themes emerged. A shared purpose, emanating from a deep sense of meaning, was the strongest reason for staying and working in a rural setting. Working in a team was second most important, with teamwork being related to attitudes and relationships, support from visiting specialists and opportunities to implement individual clinical skills. A culture of support was third, followed by opportunities for growth and continuing professional development, including teaching by outreaching specialists. The fifth theme was a healthy work-life balance.Conclusion: Health practitioners continue to work in rural settings for often deeper reasons relating to a sense of meaning, being part of a team that closely relate to each other and feeling supported.

In this issue of the SAJAA, Smith et al report on the effects of various end-tidal concentrations of nitrous oxide on the processed electroencephalogram (EEG) in the presence of approximately 1 MAC of sevoflurane. At low concentrations (10–60%), nitrous oxide had minor effects on ‘state entropy’ as measured by the M-entropy S/5 Module (GE Healthcare). However, at 70% there were statistically significant and clinically important decreases in entropy. Whereas previous studies have shown that nitrous oxide when given alone has few if any effects on EEG entropy, when administered with 1 MAC volatile anaesthetic agent, there is a threshold at which the effects of the volatile agent are potentiated by nitrous oxide. These findings are in accordance with other reports concerning studies of the clinical effects of combinations of nitrous oxide and oxygen.

Tramadol may cause awareness and EEG activation during anaesthesia. We compared tramadol with morphine, administered during wound-closure, surmising that tramadol may cause earlier awakening, more rapid recovery, less respiratory depression and equivalent pain relief. Forty patients received nitrous oxide-enflurane for abdominal surgery. At wound closure, patients received tramadol 3 mg kg-1 or morphine 0.2 mg kg-1 and end-tidal enflurane concentrations were maintained at 0.5 kPa until skin closure, whereupon anaesthesia was discontinued. Times to spontaneous respiration, awakening and orientation were similar in the two groups, as were blood-gas tensions, ventilatory frequency, pain scores and incidence of nausea. Half of each group required supplementary analgesia during their 90-min stay in the recovery room. P-deletion counts improved more rapidly in the tramadol group. This study confirms previous reports that tramadol did not antagonize the hypnotic effects of volatile anaesthetics. Tramadol, administered during operation, was as effective as morphine in providing postoperative analgesia while permitting more rapid psychomotor recovery.

Pain is now regarded as the “fifth vital sign” and pain relief to be a basic human right. Patient-controlled anaesthesia (PCA) is effective because it enables self-titration to individual requirements. PCA is perceived to be inherently safe because of the lockout interval, and because sedation purportedly stops the patient from pressing the button. Nevertheless, because of respiratory depression, increasing numbers of adverse events are serious cause for concern. Respiratory depression comprises three components: central respiratory depression, airway obstruction and sedation. Together, these effects result in opioid-induced respiratory impairment (OIVI). Strategies for safety improvement include an understanding of opioid pharmacokinetics and pharmacodynamics, appropriate dosing regimens, establishing guidelines and written orders,appropriate monitoring and record-keeping, staff training for PCA competency, preoperative patient education and oxygen administration when appropriate, e.g. sleeping patients. Initial postoperative analgesia should be established personally by the attending practitioner who should titrate small doses of opioid to the desired effect. It is emphasised that counting breathing rates is an unreliable index of OIVI is that the quality of breathing should be assessed, and that sedation occurs before OIVI, is clinically obvious. Therefore, monitoring and recording a sedation score at regular intervals is essential. During opioid administration, sedation should be regarded as the “sixth vital sign”.

Background Computer-assisted target controlled infusions (TCI) result in prediction errors that are influenced by pharmacokinetic variability among and within patients. It is uncertain whether the selection of a propofol pharmacokinetic parameter set significantly influences drug concentrations and clinical acceptability. Methods Thirty patients received similar propofol TCI regimens after being randomly allocated to one of three parameter sets. Arterial and venous concentrations were measured and prediction errors calculated from pooled and intrasubject data. Results Arterial propofol concentrations in the Dyck group revealed greater bias (mean 43%) than did those in the Marsh (-1%) and Tackley (-3%) groups. The Dyck group also showed greater inaccuracy (mean:47%) than the Marsh (29%) and Tackley (24%) groups. There was little tendency for measured concentrations to vary from targeted values over time (divergence). Variability about an observed mean in individual patients (wobble) was low. Venous propofol concentrations were initially much less than arterial concentrations, but this difference decreased over time. Conclusions Although it may be preferable to administer propofol TCI by using a locally derived parameter set, it is acceptable to use a model from elsewhere. The Marsh and Tackley models produced equally good performance and are appropriate for propofol TCI within the range of 3-6 micrograms/ml. The Dyck model was less accurate at maintaining anesthetic concentrations, possibly because it was derived from low concentrations. Concentrations in blood, the most sensitive indicators of performance, demonstrated differences among the parameter sets. Clinically, TCI worked well, and by clinical criteria, the choice of pharmacokinetic model did not appear to make a difference.

Background: It has been suggested that spectral entropy of the electroencephalogram as applied in the M-Entropy S/5TM Module (GE Healthcare) does not detect the effects of nitrous oxide (N2O). The aim of this study was to investigate the effect on entropy by graded increases in N2O concentrations in the presence of a constant concentration of sevoflurane, in the absence of surgical stimulation.Method: This single-blind, randomised study was conducted at an altitude of approximately 1 400 m. Patients received sevoflurane 2% (1.7% at sea level) and N2O, at end-tidal concentrations of 0%, 10%, 20%, 30%, 40%, 50%, 60% or 70% (equivalent to 8.5%, 17%, 25.5%, 34%, 42.6%, 51.1% and 59.6% at sea level). Entropy was measured before, during and after N2O administration. The absolute changes and ratios o f entropy relative to the baseline were calculated. Between- and within-group comparisons were made using analysis of variance and covariance.Results: None of the entropy variables differed significantly within and between groups before and after N2O administration. Within-group analysis revealed that entropy during N2O administration was significantly lower than before or after N2O administration (P < 0.007). While a minor clinical but statistically significant linear relationship was observed between increasing N2O concentration and decreasing entropy from N2O 0% to 60%, a steeper and clinically important decrease (relative change > 20%) was noted at N2O > 60% (> 51% at sea level).Conclusions: The M-Entropy Module S/5TM responds to increasing concentrations of N2O in the presence of 2% (1.7% at sea level) sevoflurane, in the absence of surgical stimulation. There is a linear relationship between increasing N2O concentrations and decreasing entropy with a steep and clinically important decrease at N2O > 60% (> 51% at sea level). The influence of ambient pressure on the partial pressures, which determine the effects of anaesthetic agents, must be taken into account. Keywords: monitoring; depth of anaesthesia; monitoring; electroencephalography; monitoring; entropy; anaesthetics volatile; sevoflurane; anaesthetic gases; nitrous oxide

BACKGROUND: With the growing use of pharmacokinetic (PK)-driven drug delivery and/or drug advisory displays, identifying the PK model that best characterizes propofol plasma concentration (Cp) across a variety of dosing conditions would be useful. We tested the accuracy of 3 compartmental models and 1 physiologically based recirculatory PK model for propofol to predict the time course of propofol Cp using concentration-time data originated from studies that used different infusion schemes.METHODS: Three compartmental PK models for propofol, called the "Marsh," the "Schnider," and the "Schuttler" models, and 1 physiologically based recirculatory model called the "Upton" model, were used to simulate the time course of propofol Cp. To test the accuracy of the models, we used published measured plasma concentration data that originated from studies of manual (bolus and short infusion) and computer-controlled (target-controlled infusion [TCI] and long infusion) propofol dosing schemes. Measured/predicted (M/P) propofol Cp plots were constructed for each dataset. Bias and inaccuracy of each model were assessed by median prediction error (MDPE) and median absolute prediction error (MDAPE), respectively.RESULTS: The M/P propofol Cp in the 4 PK models revealed bias in all 3 compartmental models during the bolus and short infusion regimens. In the long infusion, a worse M/P propofol Cp at higher concentration was seen for the Marsh and the Schuttler models than for the 2 other models. Less biased M/P propofol Cp was found for all models during TCI. In the bolus group, after 1 min, a clear overprediction was seen for all 3 compartmental models for the entire 5 min; however, this initial error resolved after 4 min in the Schnider model. The Upton model did not predict propofol Cp accurately (major overprediction) during the first minute. During the bolus and short infusion, the Marsh model demonstrated worse MDPE and MDAPE compared with the 3 other models. During short infusion, MDAPE for the Schnider and Schuttler models was better than the Upton and the Marsh models. All models showed similar MDPE and MDAPE during TCI simulations. During long infusion, the Marsh and the Schuttler models underestimated the higher plasma concentrations.CONCLUSION: When combining the performance during various infusion regimens, it seems that the Schnider model, although still not perfect, is the recommended model to be used for TCI and advisory displays. (Anesth Analg 2010;111:368-.79)

In the presence of the obligatory shunt during one-lung ventilation, arterial oxygenation is determined by the magnitude of the shunt in addition to the oxygen content of the mixed venous blood coursing through that shunt. The present discussion aims to heighten awareness of factors determining arterial oxygenation during one-lung anesthesia, other than the magnitude of the shunt and dependent lung low-ventilation perfusion units.A convenient way to increase mixed venous and thereby arterial oxygenation is to raise cardiac output. While this approach has achieved some success when increasing cardiac output from low levels, other studies have highlighted limitations of this approach when cardiac output attains very high levels. The effect of anesthesia techniques on the relationship between oxygen consumption and cardiac output could also explain unanswered questions regarding the pathophysiology of arterial oxygenation during one-lung anesthesia.The effects of anesthesia techniques on oxygen consumption, cardiac output and therefore mixed venous oxygenation can significantly affect arterial oxygenation during one-lung anesthesia. While pursuing increases in cardiac output may, under limited circumstances, benefit arterial oxygenation during one-lung ventilation, this approach is not a panacea and does not obviate the necessity to optimize dependent lung volume.

No Abstract Available Southern African Journal of Anaesthetics and Analgesia Vol.11(1) 2005: 21

Background: Haematocrit (Hct) values 18% on CPB and 33% in the ICU. Results: Hctpred bias and precision were 2.6% and 13.1%. A Hctpred cut-off value of 23% reliably forecast a HctCPB < 20% (15 patients with mean HctCPB 16.5%). Despite a 31% false positive rate (FPR), there is emphasis on safety associated with the 23% Hctpred cutoff-point. (100% negative predictive value; zero negative likelihood ratio). Applying the same predictive criterion to all blood transfusions performed in the OR, increased positive predictive values from 43% to 63% so that the FPR decreased to 24%. Autologous transfusion comprised 72% of transfused blood and was the only transfusion in 67% of patients. Banked-blood recipients weighed less and had lower pre-operative haemoglobin concentrations, Hctpred and HctCPB . They received larger transfusions of which autologous blood formed 46%. Conclusions: 1. It is possible to predict which patients will develop potentially low HctCPB . 2. Autologous transfusions result in considerable reduction of banked blood usage. Key Words: Haematocrit, Blood transfusion, Autologous, Cardiopulmonary bypass, ROC curve, Predictive value of tests Southern African Journal of Anaesthetics and Analgesia Vol.11(1) 2005: 7-13

Our aims were to evaluate the effect of sevoflurane on postcardioplegic functional recovery of the isolated rat heart including the role of the adenosine triphosphate regulated potassium (KATP) channels and to compare the cardioprotective effects of equipotent concentrations of halothane and sevoflurane. Isolated perfused rat hearts were subjected to 45 or 60 min normothermic cardioplegic arrest and 30 min reperfusion. Sevoflurane (0.9% and 1.7%), halothane (0.4% and 0.8%), or sevoflurane (0.9%) plus glibenclamide (10 μM) (a KATP channel blocker) were administered at different time intervals. Measurements of mechanical activity were made before and after arrest. Function during reperfusion after cardioplegic arrest was significantly depressed in both untreated and treated hearts. However, sevoflurane administered both before and after arrest, or before only, significantly improved functional recovery after 45 min of cardioplegia. This protective effect was abolished by simultaneous administration of glibenclamide, suggesting a role of the KATP channel. Sevoflurane was as effective as halothane in improving postcardioplegic functional performance. After 45 min of arrest, hearts exposed to either anesthetic at both concentrations had a significantly higher work performance on discontinuation of their administration than untreated controls. After 60 min of arrest, neither anesthetic elicited protection. In view of the possible significance for volatile anesthetics in cardiac surgery, the effects of sevoflurane and halothane were compared on postcardioplegic recovery of rat hearts. Both anesthetics were equally effective in improving functional recovery after normothermic cardioplegic arrest. Sevoflurane’s beneficial effects were abolished by glibenclamide, suggesting a role for the adenosine triphosphate regulated potassium channel.

Halothane offers protection against the reperfusion injury of the myocardium. This study compared sevoflurane with halothane in its potential to modulate the effects of acute severe ischemia and reperfusion on the myocardium. Experiments were conducted on 25 pigs. Anesthesia consisted of thiopental, vecuronium and fentanyl. The lungs were mechanically ventilated with oxygen and nitrogen. Animals were randomly allocated to receive either I MAC halothane or sevoflurane. A control group received fentanyl and pentobarbital. Regional myocardial function was measured with sonomicrometers. The left anterior descending coronary artery was occluded for 15 min followed by 60 min reperfusion. Neither halothane nor sevoflurane protected the heart against the effects of acute and severe regional myocardial ischemia. During reperfusion, 89% of the animals receiving sevoflurane suffered from ventricular fibrillation compared with 30% in the halothane group (P < 0.005). Five minutes into the reperfusion period the animals subjected to halothane anesthesia demonstrated an 88% recovery in regional myocardial systolic function while in the sevoflurane group the recovery was 40% of pre-ischemic control (P < 0.05). Halothane is associated with less reperfusion arrhythmias and, in addition, recovery of regional myocardial function during reperfusion was more rapid in the presence of halothane than with sevoflurane.

We have studied 51 patients who were anaesthetized with propofol and suxamethonium followed by 0.7% isoflurane and 66% nitrous oxide in oxygen to see if tramadol caused lightening of anaesthesia. A two-channel EEG was recorded and music was played via headphones. Two groups received tramadol 200 and 100 mg i.v. and the third group received saline. Tramadol caused significant, dose-dependent activation of the EEG, evidenced by increased frequencies and decreased amplitudes, but these changes were small and probably unimportant. Derived EEG variables did not approach values known to be associated with near-awakening during isoflurane anaesthesia. No patient moved on skin incision and there were no incidences of free recall.

The use of generic pharmaceutical agents is entrenched in South Africa, with resource limitation being the primary motivation. The clinical efficacy, in vivo performance and subsequently the role of generic antimicrobial formulations in treating serious bacterial infections, is much debated. 1 We evaluated the in vitro microbiological efficacy of a generic ceftriaxone product against several clinically significant organisms collected from sterile sites. The minimum inhibitory concentration (MIC) of each was determined simultaneously with the reference and the generic ceftriaxone product. Comparative analysis of MICs between the two products for each isolate was performed using both categorical (interpretive) agreement and essential (actual MIC value) agreement. A total of 260 isolates were tested. Overall, there was categorical agreement of 98.9% and essential agreement of 95.8%. The categorical agreement for all isolates (96.7 - 100%) accorded with international standards, as no very major errors were seen and the major error rate was less than 3%. Of the 90 isolates of E. coli (40), Klebsiella spp. (40) and Salmonella spp. (10), 87.6% had an MIC less than or equal to 0.12 mg/l. The generic ceftriaxone product showed equivalent efficacy by MIC determination to the reference formulation. Ceftriaxone remains a viable and useful antimicrobial agent against a variety of clinically relevant organisms in our setting.