Masters Degrees (Anaesthesiology and Critical Care)

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Browsing Masters Degrees (Anaesthesiology and Critical Care) by browse.metadata.advisor "Levin, Andrew I."

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    The ability of the thromboelastogram (TEG® R-time difference between kaolin and heparinase) as a point of care test to predict residual heparin activity after in vitro protamine titration
    (Stellenbosch : Stellenbosch University, 2017-12) Joseph, Lauren Ann; Levin, Andrew I.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Anaesthesiology and Critical Care.
    ENGLISH ABSTRACT: Background: Differentiation between surgical bleeding and coagulopathy is critical as re-exploration is associated with increases in mortality and morbidity. Adequate reversal of heparin with protamine at the end of cardiopulmonary bypass (CPB) is critical to prevent postoperative bleeding. Meticulous dosing of protamine is required as excessive dosages has deleterious side effects on clotting. Traditional methods make use of an activated clotting time (ACT) for evaluation of adequate heparin reversal. However, recent use of other point of care (POC) tests, the thromboelastogram (TEG®) has started challenging the utility and exclusive use of ACT to evaluate effective reversal. Differences between thromboelastographic Rkaolin and R-heparinase times is an indicator of residual heparin. However, the exact relationship between these parameters and the exact amount of residual heparin is unknown. The rationale for this study was to accurately determine the relationship between the magnitude of the R-kaolin and R-heparinase time difference and blood heparin concentrations. Aims: This study was performed to define the in-vitro relationship between the difference between the thromboelastographic R-kaolin and R-heparinase time difference (TEG® Delta-kh R-time) and plasma heparin concentrations. The primary outcome was to determined the relationship between the TEG® Delta-kh R-time difference and heparin concentrations. The secondary outcome was to determine the concentration of heparin at or below which R-kaolin times become measureable. Methods: This was a single centre, prospective, randomized laboratory study. Following institutional ethics approval and informed consent, sixty-two samples were taken during CPB from 20 patients meeting inclusion criteria. Samples were randomized to one of three groups which would dictate the protamine dose. The three groups were based on a protamine to heparin ratio (expressed as milligram protamine per milligram heparin administered to the patient) approximating 0.25, 0.5, and 0.75 mg/mg respectively. Each sample of blood was then administered a dose of protamine. The TEG® analysis entailed measuring the R-kaolin and R-heparinase time and noting the difference. Thereafter, each blood sample was sent for heparin concentration determination using an anti-Xa activity assay. Results: No relationship between the measurable R-kaolin time and heparin concentration could be demonstrated (p=0.80), as well as no relationship between measurable TEG® Delta-kh R- time difference and heparin activity (p=0.42). However, we did identify a high probability to be able to predict a measurable R-kaolin time (negative predictive value 90%, 95% CI 74% to 98%) when heparin concentration is less than 1.24IU/ml. Conclusions: We were unable to predict heparin concentration using TEG® in this study. It is likely that this was related to methodological problems. The protamine dose was a complex calculation and there is uncertainty with regard to the actual amounts used. There were also multiple laboratory technicians, with a possible loss of standardization. However, R-kaolin time will likely be measurable at heparin concentrations below 1.24 IU/ml, and not measurable above that value. This observation is immensely valuable for clinicians and researchers. Future studies should take this into account and attempt to determine the relationship between TEG® Delta-kh R- time differences and heparin activity only when heparin concentration are less than 1.24IU/ml.
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    Comparison of minimally and more invasive methods of determining mixed venous oxygenation
    (Stellenbosch : Stellenbosch University, 2013-12) Smit, Marli; Levin, Andrew I.; Coetzee, J. F.; Stellenbosch University. Faculty of Medicine & Health Sciences. Dept. of Anesthesia and Critical Care.
    ENGLISH ABSTRACT: Circulatory efficiency is the relationship between oxygen consumption and global oxygen delivery. Manipulation of circulatory efficiency has been shown to be beneficial in critically ill surgical and medical adults, and in children. Circulatory efficiency is best assessed by measuring an index of mixed venous oxygenation (content, saturation and partial pressure) and viewing this in the context of oxygen consumption. Mixed venous oxygenation has until now required intermittent sampling via a pulmonary artery catheter, or by using a pulmonary artery catheter equipped with a fibre optic bundle for continuous mixed venous oxygen saturation monitoring. However, the use of the pulmonary artery catheter is declining as it has been (correctly or incorrectly) indicted of being an “invasive” tool. Attempts have been made to estimate mixed venous oxygenation non-invasively using the “NICO” monitor[6], near infrared spectroscopy[7], skeletal muscle oxygen saturation[8], thenar muscle oxygen saturation[9] and transtracheal pulse oximetry.[4]While all of them effectively trended mixed venous oxygen saturation, their accuracy and use as a resuscitation endpoint are in doubt. Sampling central venous as a surrogate of mixed venous oxygenation is fraught with problems, particularly in sicker patients. Significant differences in oxygenation can be demonstrated between the pulmonary arterial and central venous sampling sites in shock states,[3, 10] in acutely ill post-surgical patients [11] and under varying hemodynamic conditions.[12] With the decline in the use of the pulmonary artery catheter, minimally invasive cardiac output determination is becoming increasingly popular. Apart from that their accuracy (particularly un-calibrated devices) has been questioned; they also cannot determine mixed venous oxygen saturation. To obtain a more reliable and refined, but less invasive, estimate of mixed venous oxygenation would be beneficial. The primary aim of this study was therefore to investigate whether venous oxygenation (mixed venous oxygen content, saturation and partial pressure) could be accurately predicted by minimally invasive methods of determining cardiac output and non-invasive calorimetric methods of measuring oxygen consumption. The methods compared were the current invasive gold standard represented by direct sampling of mixed venous blood and thermodilution cardiac output using a pulmonary artery catheter, with a less invasive method of calculating mixed venous saturation, the latter comprised of 4 elements: 1. Cardiac output was measured using a minimally invasive technique, namely lithium dilution (LiDCo®). 2. Oxygen consumption was measured with a non-invasive calorimetric device (M-COVX™ module manufactured by General Electric Corporation). 3. Arterial oxygen content was estimated using blood sampled via an arterial catheter. 4. These 3 variables were inputted into Fick’s equation and solved for venous oxygen content (CvO2 = CaO2 –VO2/CO). Thereafter, using the calculated venous oxygen content as well as the haemoglobin concentration, mixed venous oxygen saturation and partial pressure was estimated using an Excel® spreadsheet (Appendix G) relating oxygen saturation and partial pressure using standard oxygen dissociation curve formula, and calculating oxygen content from various haemoglobin concentrations. Analysis of the data was performed predominantly using Bland Altman analysis. LiDCo® derived cardiac output overestimated that measured using intermittent thermodilution PAC by a clinically significant average of 0.82liters/minute or 26%. The pulmonary artery catheter derived oxygen consumption underestimated that measured by the metabolic module by 52 ml/minute or 27%. Oxygen consumption was the parameter having the largest percentage error (27%) and difference between the Bland Altman upper and lower limits of agreement. The difference between oxygen consumption measured by indirect calorimetry is expected to exceed that calculated using the indirect Fick method by 20 to 30% because intra-pulmonary oxygen consumption is excluded when using this method.[ 13] However, the scatter exhibited by the calorimetry estimations of oxygen consumption was probably the major reason for the discrepancy between the calculated and measured mixed venous oxygenation variables. Despite small (12.0 to 26.3 %) differences between measurements in individual patients, venous oxygenation variables measured by the invasive and less invasive techniques were statistically different. We also considered the magnitude of these differences to be clinically significant as we were of the opinion that relying on the calculated results could adversely impact clinical decision-making. In conclusion, we could not estimate venous oxygenation accurately enough using minimally invasive methods of determining cardiac output and non-invasive methods of measuring oxygen consumption to be clinically useful.
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    The effect of high dose morphine compared to fentanyl infusion on serum levels of mast cell tryptase during cardiac surgery
    (Stellenbosch : Stellenbosch University, 2016-12) Barbieri, Mia; Levin, Andrew I.; Stellenbosch University. Faculty of Health Sciences. Dept. of Anaesthesiology and Critical Care.
    Background: Morphine directly activates cutaneous mast cells in a seemingly dose-dependent manner, resulting in the release of both histamine and tryptase into the bloodstream. Tryptase is almost exclusively stored in mast cells. Elevated serum tryptase concentrations serve as an indicator of mast cell activation and have become the most frequently used laboratory investigation in anaphylaxis. Following a clinical diagnostic dilemma our study was aimed at answering whether mast cell tryptase concentration remains useful in supporting the diagnosis of anaphylaxis even after administration of high dose morphine. Methods:We conducted a non-blinded, randomized controlled trial comparing the effects of fentanyl and high dose morphine, on serum mast cell tryptase concentrations. A power analysis was performed. Twenty adults undergoing cardiac surgery were randomly assigned to one of two opioid regimens. Both groups received a fentanyl bolus of 3 to 8 mcg/kg at induction. In the fentanyl group this was followed by a fentanyl infusion of 5 to 10 mcg/kg/hr until completion of surgery. Patients in the morphine group received morphine 1 mg/kg infused over thirty minutes. Baseline serum mast cell tryptase concentrations were determined directly prior to induction of anaesthesia and again 90 minutes after the start of the opioid infusion. The primary endpoint was statistical differences in tryptase concentrations between the morphine and fentanyl groups at the two time periods. Results: Ten patients of similar demographics were enrolled in each group. In the fentanyl group the second, 90-minute mast cell tryptase concentration was statistically significantly (10.1%) lower (p = 0.006) than baseline. Despite the 95% confidence interval of the difference between the means (-1.06 to -0.34 mcg/L) not including zero , this was not a clinically important difference. In the morphine group serum mast cell tryptase concentrations in the second (90 minute) sample were not statistically different from baseline values, the 95% confidence interval including zero. No between-group differences in tryptase concentration were detected. One patient in the morphine group exhibited a clinically significant 50,4% increase in tryptase concentrations, albeit from a high baseline of 11.9 mcg/L, which in this small study constitutes a prevalence of 10% (95% CI 1.8% to 40.4.) Conclusion: In this small pilot study, serum mast cell tryptase concentrations were unaffected by whether fentanyl or high dose morphine was administered. The null hypothesis, that there is no significant increase in serum mast cell concentrations after high dose morphine compared to fentanyl during cardiac anaesthesia and surgery, was therefore accepted. Larger studies are however needed to ensure a robust result, especially in the morphine group