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S T Robinson

Publications and source records attributed to S T Robinson.

9 recordsLinked to original sources

Oxygen metabolism during liver transplantation: the effect of dichloroacetate.

UNLABELLED: Dichloroacetate (DCA) stimulates pyruvate dehydrogenase (PDH), accelerating recovery of the postischemic heart. Because DCA also stimulates hepatic PDH, it may facilitate graft recovery during liver transplantation (OLT). Hepatic removal and replacement during OLT produce major changes in O2 consumption (VO2), and return of baseline VO2 has been used to index early graft function. We examined the effect of DCA on O2 metabolism during OLT. Forty patients received DCA 80 mg/kg intravenously in divided doses, and 40 served as controls. Serial measurements were made for body temperature, hemodynamics, O2 metabolic indices, and plasma substrate and hormonal concentrations. Oxygen delivery (DO2I) and consumption (VO2I) indices were calculated. Patients exhibited stable hemodynamics, with similar fluid and blood product requirements. Compared with the dissection stage, DO2I and VO2I were decreased during the anhepatic stage (31% and 36%, respectively), then returned to dissection stage values soon after portal vein unclamping. Temperature decreased during the anhepatic stage and returned toward dissection stage value after graft perfusion. DCA reduced lactic acidosis and NaHCO3 use but did not alter hemodynamics or measures of O2 metabolism or body temperature. VO2 is decreased during the anhepatic stage largely due to loss of hepatic metabolism. Restoration of VO2 by 30 min after portal vein unclamping reflects rapid recovery of O2 metabolism by the graft liver, but DCA does not accelerate recovery of VO2. DCA does not seem to facilitate early graft hepatic function as indexed by VO2. IMPLICATIONS: We evaluated whether dichloroacetate, which stimulates pyruvate dehydrogenase, can accelerate recovery of graft liver hepatic function during liver transplantation, as indexed by oxygen consumption. We found that despite evidence that it activated pyruvate dehydrogenase, dichloroacetate did not affect recovery of transplanted liver function.

Acid-Base Equilibrium↗

Amelioration of lactic acidosis with dichloroacetate during liver transplantation in humans.

BACKGROUND: Marked lactic acidosis occurs during orthotopic liver transplantation (OLT), especially during the anhepatic phase. Current standard therapy is NaHCO3, although it may exacerbate intracellular acidosis, increase plasma lactate, and contribute to hypernatremia. Alternatively, dichloroacetate (DCA) stimulates pyruvate oxidation in vivo, reduces plasma lactate, and moderates intracellular acidosis. The aims of this study were to test the efficacy of DCA to control lactic acidosis, reduce the NaHCO3 requirement and incidence of hypernatremia, and stabilize perioperative acid-base homeostasis. Others aims were to examine the DCA pharmacokinetic profile during OLT and the role of lactate metabolism in OLT-associated hyperglycemia. METHODS: Patients (n = 66) for OLT were divided into two equal groups to receive or not receive DCA during OLT. DCA 40 mg.kg-1 was infused over 60 min after induction of anesthesia and 4 h later. Plasma DCA concentration was measured by gas chromatography-mass spectroscopy, and pharmacokinetics were assessed by a one-compartment model. Serial arterial blood gases, lactate, Na+, glucose, and hemodynamic measurements were compared, as were intraoperative utilization of blood products, CaCl2, and NaHCO3. RESULTS: Plasma DCA concentration was maintained between 0.28 and 1.18 mM during OLT, with peak concentrations of 0.73 +/- 0.06 (mean +/- SE) and 1.18 +/- 0.09 mM, respectively after the first and second doses. In control patients, plasma lactate was 1.07 +/- 0.04 at baseline and 1.20 +/- 0.06 before incision and reached a peak of 7.30 +/- 0.41 mM after graft reperfusion. In DCA-treated patients, the respective values were 1.07 +/- 0.06 (difference not significant), 0.63 +/- 0.05 (P < 0.001), and 3.39 +/- 0.20 (P < 0.001) mM. Intraoperative changes in arterial blood pH, HCO3(-1), and base excess were comparable though less marked in DCA-treated patients, whose NaHCO3 requirement was reduced (0.59 +/- 0.36 vs. 2.83 +/- 0.53 mEq.kg-1 in control patients, P < 0.001). There was no difference between groups in requirements for CaCl2 or blood products, in intraoperative hemodynamics, in duration of the surgical stages, or in graft ischemia times. Twelve control and 4 DCA-treated patients exhibited a plasma Na+ concentration > 145 mEq/1 at completion of surgery (P < 0.05). Hyperglycemia was not attenuated by DCA despite decreased plasma lactate concentration. Sixteen and 28 h after graft reperfusion, when plasma DCA had been eliminated, plasma lactate and degree of metabolic alkalosis did not differ between groups. CONCLUSIONS: DCA safely and effectively attenuated lactic acid accumulation and moderated acidosis during OLT. DCA decreased the requirement for NaHCO3 therapy and the incidence of hypernatremia. OLT-associated hyperglycemia did not result from lactate-induced stimulation of hepatic gluconeogenesis. Postoperative metabolic alkalosis was not substantially influenced by lactate metabolism.

Acidosis, Lactic↗

The hemodynamic effects of intraoperative injection of muromonab CD3.

During anesthesia 5 mg of muromonab CD3 (OKT3), an anti-CD3 monoclonal antibody, was administered prophylactically to twelve patients undergoing cadaveric renal transplantation. Preoperatively, all patients were at or near their dry body weights. Methylprednisolone 500 mg on call to or in the operating room, azathioprine 2 mg kg-1 and diphenhydramine 50 mg were administered intraoperatively to reduce the probability and severity of reported effects of OKT3. After induction of anesthesia, the patients were monitored for changes in cardiovascular variables for up to 120 min after OKT3 administration. All patients had uneventful anesthetic courses. Analysis of variance showed no significant changes from pre-OKT3 administration in heart rate, mean blood pressure, mean pulmonary artery pressure, central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), and pulmonary vascular resistance (PVRI). CVP values were a reliable indicator of PCWP with the correlation coefficient of CVP to PCWP or r = 0.78 (P < 0.00005) and PCWP = .89 x CVP + 3.78. Cardiac index (CI) increased 22% at 105 min (P < 0.05). Systemic vascular resistance index (SVRI) decreased 21% at 105 min (P < 0.05). SVRI was increased 16% at 10 min post-OKT3 (P < 0.05). All of these statistically significant values were within acceptable clinical limits. Euvolemic cadaveric renal transplant recipients receiving prophylactic steroids and diphenhydramine may receive OKT3 in the operating room for induction immunosuppression without any appreciable risk of cardiovascular compromise.

Anesthesia↗

Role of industrial hygiene in medical surveillance.

The industrial hygienist and the occupational physician comprise a team that can effectively recognize and evaluate employee exposures to workplace-generated contaminants. At the most basic level, the industrial hygienist performs the exposure assessment, and the occupational physician develops the medical surveillance program. The actual mechanisms for assessing employee exposures and ultimately implementing a medical surveillance program are complex and are detailed in this paper.

Environmental Monitoring↗