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Biomedical subjects

A M De Wolf

Publications and source records attributed to A M De Wolf.

At least 19 recordsLinked to original sources

Large volume N2O uptake alone does not explain the second gas effect of N2O on sevoflurane during constant inspired ventilation.

BACKGROUND: The second gas effect (SGE) is considered to be significant only during periods of large volume N(2)O uptake (VN(2)O); however, the SGE of small VN(2)O has not been studied. We hypothesized that the SGE of N(2)O on sevoflurane would become less pronounced when sevoflurane administration is started 60 min after the start of N(2)O administration when VN(2)O has decreased to approximately 125 ml min(-1), and that the kinetics of sevoflurane under these circumstances would become indistinguishable from those when sevoflurane is administered in O(2). METHODS: Seventy-two physical status ASA I-II patients were randomly assigned to one of six groups (n=12 each). In the first four groups, sevoflurane (1.8% vaporizer setting) administration was started 0, 2, 5 and 60 min after starting 2 litre min(-1) O(2) and 4 litre min(-1) N(2)O, respectively. In the last two groups, sevoflurane (1.8 or 3.6% vaporizer setting) was administered in 6 litre min(-1) O(2). The ratios of the alveolar fraction of sevoflurane (Fa) over the inspired fraction (Fi), or Fa/Fi, were compared between the groups. RESULTS: Sevoflurane Fa/Fi was larger in the N(2)O groups than in the O(2) groups, and it was identical in all four N(2)O groups. CONCLUSIONS: We confirmed the existence of a SGE of N(2)O. Surprisingly, when using an Fa of 65% N(2)O, the magnitude of the SGE was the same with large or small VN(2)O. The classical model and the graphical representation of the SGE alone should not be used to explain the magnitude of the SGE. We speculate that changes in ventilation/perfusion inhomogeneity in the lungs during general anaesthesia result in a SGE at levels of VN(2)O previously considered by most to be too small to exert a SGE.

Adolescent↗

Air-oxygen mixtures in circle systems.

STUDY OBJECTIVE: To determine the effect of different air-O(2) mixtures and fresh gas flows (FGF) on the relationship between the delivered (F(Del)O(2)) and inspired O(2) fraction (FIO(2)) in a circle system. STUDY DESIGN: Randomized clinical study. SETTING: Large teaching hospital. PATIENTS: 160 ASA physical status I, II, and III patients undergoing a variety of cardiovascular procedures with general endotracheal anesthesia. INTERVENTIONS: 160 patients were randomly assigned to one of 20 groups (n = 8 each), depending on the combination of total FGF (0.5, 1, 2, 4, or 8 L/min) and air-O(2) mixture used (ratios of 4/1, 3/2, 2/3, or 1/4), corresponding to a F(Del)O(2) of 0.37, 0.53, 0.68, and 0.84. For each combination of FGF and air-O(2) mixture, FIO(2) after equilibration was compared with F(Del)O(2). MEASUREMENTS AND MAIN RESULTS: With any air-O(2) mixture with a FGF < or = 2 L/min, FIO(2) became lower than F(Del)O(2). Because FIO(2) decreased below 0.25 after 13 and 26 minutes in the first two patients of the 4/1 0.5 L/min air-O(2) group, this study limb was terminated. CONCLUSIONS: When using air-O(2) mixtures in a circle system, FIO(2) becomes lower than the F(Del)O(2) with FGF < or = 2 L/min. The relative proportion of O(2) in the FGF has to be increased accordingly.

Air↗

Intracardiac thrombus formation and pulmonary thromboembolism immediately after graft reperfusion in 7 patients undergoing liver transplantation.

Intravascular and/or intracardiac thrombus formation followed by pulmonary thromboembolism with right ventricular dysfunction immediately after graft reperfusion during orthotopic liver transplantation (OLT) is described in 7 patients. This complication may have been related to excessive activation of the coagulation system by graft reperfusion, which overwhelmed anticoagulation mechanisms and was disproportionate to fibrinolysis. Activation of the coagulation system may be more pronounced in patients who receive less than optimal grafts, require massive transfusion, or have septic complications at the time of OLT. It is unclear whether antifibrinolytic therapy during the anhepatic stage had a role. Transesophageal echocardiography was useful in diagnosing and managing intracardiac thrombus and pulmonary thromboembolism.

Adult↗

The ADU vaporizing unit: a new vaporizer.

UNLABELLED: We determined the performance of the vaporizer of the ADU machine (Anesthesia Delivery Unit; Datex-Ohmeda, Helsinki, Finland). The effects of carrier gas composition (oxygen, oxygen/N(2)O mixture, and air) and fresh gas flow (0.2 to 10 L/min) on vaporizer performance were examined with variable concentrations of isoflurane, sevoflurane, and desflurane across the whole range of each vaporizer's output. In addition, the effects of sudden changes in fresh gas flow and carrier gas composition, back pressure, flushing, and tipping were assessed. Vaporizer output depended on fresh gas flow, carrier gas composition, dial settings, and the drug used. Vaporizer output remained within 10% of dial setting with fresh gas flows of 0.3-10 L/min for isoflurane, within 10% of dial setting with fresh gas flows of 0.5-5 L/min for sevoflurane, and within 13% of dial setting with fresh gas flows of 0.5 to 1 L/min for desflurane. Outside these fresh gas flow ranges, output deviated more. The effect of sudden changes in fresh gas flow or carrier gas composition, back pressure, flushing, and tipping was minimal. We conclude that the ADU vaporizer performs well under most clinical conditions. Despite a different design and the use of complex algorithms to improve accuracy, the same physical factors affecting the performance of conventional vaporizers also affect the ADU vaporizer. IMPLICATIONS: The ADU vaporizer performs well under most clinical conditions. Despite a different design and the use of complex algorithms to improve accuracy, the same physical factors affecting the performance of conventional vaporizers also affect the ADU vaporizer.

Anesthesiology↗

The pharmacokinetics of dexmedetomidine in volunteers with severe renal impairment.

UNLABELLED: Dexmedetomidine, an alpha2-adrenergic agonist with sedative and analgesic properties, is mainly cleared by hepatic metabolism. Because the pharmacokinetics of dexmedetomidine have not been determined in humans with impaired renal function, we studied them in volunteers with severe renal disease and in control volunteers. Six volunteers with severe renal disease and six matched volunteers with normal renal function received dexmedetomidine, 0.6 microg/kg, over 10 min. Venous blood samples for the measurement of plasma dexmedetomidine concentrations were drawn before, during, and up to 12 h after the infusion. Two-compartmental pharmacokinetic models were fit to the drug concentration versus time data. We also determined its hemodynamic, respiratory, and sedative effects. There was no difference between Renal Disease and Control groups in either volume of distribution at steady state (1.81 +/- 0.55 and 1.54 +/- 0.08 L/kg, respectively; mean +/- SD) or elimination clearance (12.5 +/- 4.6 and 8.9 +/- 0.7 mL x min(-1) x kg(-1), respectively). However, elimination half-life was shortened in the Renal Disease group (113.4 +/- 11.3 vs 136.5 +/- 13.0 min; P < 0.05). A mild reduction in blood pressure occurred in most volunteers. Although most volunteers were sedated by dexmedetomidine, renal disease volunteers were sedated for a longer period of time. IMPLICATIONS: The pharmacokinetics of dexmedetomidine in volunteers with severe renal impairment differed little from those in volunteers with normal renal function. In addition, there were no clinically significant differences in the hemodynamic responses to dexmedetomidine. However, dexmedetomidine resulted in more prolonged sedation in subjects with renal disease.

Adrenergic alpha-2 Receptor Agonists↗

Coasting after overpressure induction with sevoflurane.

STUDY OBJECTIVE: To evaluate the clinical feasibility of using a coasting technique to temporarily maintain anesthesia after overpressure induction with sevoflurane. STUDY DESIGN: Prospective clinical study. SETTING: Large teaching hospital. PATIENTS: 12 ASA physical status I, II, and III patients receiving general anesthesia for a variety of peripheral procedures. INTERVENTIONS: After overpressure induction of anesthesia with sevoflurane (8%) in an O(2)/N(2)O mixture, the fresh gas flow (FGF) was lowered to 0.5 L/min and the vaporizer was turned off (coasting). MEASUREMENTS AND MAIN RESULTS: After priming a circle system with sevoflurane (8% sevoflurane vaporizer setting in 6 L/min O(2)/N(2)O [33%/66%] for 30 s), patients took several vital capacity breaths from the mixture until loss of consciousness. After 3.4 +/- 0.7 min, depth of anesthesia was considered adequate for laryngeal mask airway (LMA) insertion, and FGF was reduced to 0.5 L/min (33% O(2), 66% N(2)O) and the sevoflurane vaporizer was turned off. The end-expired sevoflurane concentration (Et(sevo)) decreased from 5.8 +/- 1.3% just before insertion of the LMA to 0.97 +/- 0.22% at 20 minutes. CONCLUSIONS: After overpressure induction with sevoflurane, coasting during minimal flow anesthesia (FGF 0.5 L/min) is a simple technique that can maintain anesthesia for short procedures (less than 15 to 20 min), or can be used as a bridge or an adjunct to other low-flow techniques.

Adult↗

Maintaining sevoflurane anesthesia during low-flow anesthesia using a single vaporizer setting change after overpressure induction.

STUDY OBJECTIVE: A sevoflurane vaporizer dial setting of 1.9% was previously found to maintain the end-expired sevoflurane concentration (Et(sevo)) at 1.3% during maintenance of anesthesia for procedures up to one hour with an O(2) FGF of 1 L/min. We examined whether applying these parameters could simplify low-flow sevoflurane anesthesia after overpressure induction using two slightly different techniques. DESIGN: Prospective clinical study. SETTING: Large teaching hospital. PATIENTS: Sixteen patients receiving general anesthesia for a variety of peripheral procedures. INTERVENTIONS: Anesthesia was induced with overpressure with sevoflurane (8%) in an 8 L. min(-1) O(2)/N(2)O mixture (30%/70%). After a laryngeal mask airway (LMA) was placed, fresh gas flow (FGF) was lowered to 1 L. min(-1) using O(2) and N(2)O (FiO(2) 30%) with patients breathing spontaneously. In group I patients (n = 8), the vaporizer dial was set at 1.9% at the same time the FGF was lowered. In group II patients (n = 8), the vaporizer was turned off until Et(sevo) had decreased to 1.3%, after which the dial was set at 1.9%. The course of Et(sevo) in the two groups was examined. MEASUREMENTS AND MAIN RESULTS: In group I, Et(sevo) after 3 min was 4.88 +/- 1. 12%. Et(sevo) decreased slowly after reduction of FGF to 1.83 +/- 0. 19%, 1.59 +/- 0.18%, and 1.52 +/- 0.19% at 10, 20, and 30 min, respectively. In group II, Et(sevo) after 3 min was 4.34 +/- 0.84%, and decreased more rapidly after reduction of FGF to 1 L. min(-1) than in group I. Et(sevo) was 1.40 +/- 0.09%, 1.40 +/- 0.11%, and 1. 38 +/- 0.13% at 10, 20, and 30 min, respectively. CONCLUSIONS: After high-flow overpressure induction with sevoflurane, a single change in vaporizer setting (to 1.9%) and FGF (to 1 L. min(-1)) suffices for the Et(sevo) to approach the predicted Et(sevo) (1.3%) within 10-15 min; thereafter the Et(sevo) remains nearly constant. As expected, the predicted Et(sevo) is attained slightly faster when the vaporizer is temporarily turned off. Clinically applying previously derived pharmacokinetic parameters simplifies low-flow sevoflurane anesthesia after overpressure induction.

Adult↗

Sevoflurane pharmacokinetics: effect of cardiac output.

Sevoflurane uptake (Vsevo) can be predicted by the square root of time model or the four-compartment model. However, Vsevo and the effect of cardiac output on anaesthetic uptake have not been quantified clinically. After obtaining IRB approval and informed consent, 34 adult patients received closed-circuit anaesthesia with sevoflurane for 1 h. The end-expired sevoflurane concentration was maintained at 2.6% by infusion of liquid sevoflurane into the breathing system. In a subgroup of 12 patients, cardiac output was measured every 5 min by thermodilution (CO group). The effect of patient characteristics (age, height, weight, body surface area) and cardiac output on Vsevo were determined, and Vsevo was compared with the theoretical models. In the CO group, measured cardiac output was used in the formulae of these models. A two-exponential curve described average Vsevo well: Vsevo (ml liquid) = 0 + 1.62 x (1 - e(-2.3)xt) + 18.1 x (1 - e(-0.0089xt), r2 > 0.999. There was no correlation between Vsevo and patient characteristics, except that Vsevo was greater in patients with a greater cardiac output (r2 = 0.36) and cardiac index (r2 = 0.35). The rate of sevoflurane uptake decreased less than predicted by the square root of time and four-compartment models, even when measured cardiac output was used in the formulae. These findings confirm that the square root of time and four-compartment models do not accurately predict anaesthetic uptake. In addition, uptake of sevoflurane cannot be predicted by patient characteristics but was higher in patients with a higher cardiac output.

Adolescent↗

Coronary artery spasm during anesthesia for liver resection.

Intraoperative coronary artery spasm (CAS) is rare, and most cases have been reported during cardiac surgery (4, 7, 12). The following is a case report of a patient undergoing liver resection developing CAS, resulting in well-documented ST-segment elevation in lead II and V5 of the electrocardiogram (ECG) and severe hemodynamic instability. The coronary spasm was successfully treated with intravenous nitroglycerin. Postoperatively, a coronary angiogram documented CAS in the absence of significant coronary artery disease, confirming the clinical diagnosis of CAS.

Anesthesia, Intravenous↗

Uptake of desflurane and isoflurane during closed-circuit anesthesia with spontaneous and controlled mechanical ventilation.

Although theoretical models predict uptake of inhaled anesthetics during closed-circuit anesthesia (CCA), clinical data for most anesthetics are conflicting or non-existent. In addition, the effects of patient characteristics and mode of ventilation on anesthetic uptake are unclear. Forty-one ASA physical status I or II adult patients undergoing a variety of 1-1.5 h surgical procedures were randomly allocated to receive CCA with desflurane or isoflurane with ventilation being either spontaneous or controlled. An end-expired anesthetic concentration of 1.3 minimum alveolar anesthetic concentration (MAC) was maintained by continuous injection of the liquid anesthetic into the circuit using a syringe pump. After an initial 4-min wash-in period, uptake during the first hour of CCA was nearly constant. Uptake was the same whether ventilation was spontaneous or controlled. Patient characteristics (age, height, weight, weight3/4, and body surface area) were comparable between groups and did not correlate with uptake. The virtually constant uptake after wash-in of desflurane and isoflurane contrasts with the square root of time model of Lowe and Ernst. These findings may greatly simplify CCA.

Adult↗

Hemodynamic effects of inhaled nitric oxide in four patients with severe liver disease and pulmonary hypertension.

Patients with moderate and severe pulmonary hypertension have a very high mortality rate when undergoing orthotopic liver transplantation. Because nitric oxide has been successful in reducing pulmonary artery pressures in certain patients with pulmonary hypertension, the efficacy of NO inhalation (40 and 80 ppm) in 4 patients with pulmonary hypertension associated with liver disease was determined. No clinically significant changes in pulmonary artery pressures or other hemodynamic parameters were observed using either concentration of NO. In conclusion, no pulmonary vasodilatory response from inhalation of NO in 4 patients with severe liver disease and pulmonary hypertension was found.

Adult↗

Ionized hypomagnesemia in patients undergoing orthotopic liver transplantation: a complication of citrate intoxication.

Using a new ion-selective electrode, plasma concentration of ionized magnesium was measured in nine adult patients undergoing orthotopic liver transplantation. Baseline plasma ionized magnesium (IMg2+) concentration (0.49 +/- 0.07 mmol/L) was slightly below normal values (0.55-0.66 mmol/L, 95% CI): Six patients had ionized hypomagnesemia and two of these had total hypomagnesemia. Ionized IMg2+ concentration progressively decreased during the dissection (0.45 +/- 0.07 mmol/L, p < 0.05) and anhepatic stage (0.38 +/- 0.07 mmol/L, p < 0.05) and returned toward baseline values by 2 hours after graft reperfusion. Plasma ionized calcium levels and acid-base status were maintained within normal limits during surgery. Serum citrate concentration increased during the dissection (0.58 +/- 0.60 mmol/L) and anhepatic stages (1.18 +/- 0.78 mmol/L), the result of transfusion of citrate-rich blood products in the absence of adequate hepatic function, and gradually returned toward baseline values after graft reperfusion. IMg2+ concentration inversely correlated with the plasma citrate concentration (r2 = 0.54). The results of this study demonstrate that ionized hypomagnesemia invariably occurs during liver transplantation and suggest that this derangement may be a clinical concern, because magnesium is an important cofactor for the maintenance of cardiovascular homeostasis. The data further suggest the clinical importance of supplementation with magnesium based on the monitoring of plasma IMg2+ concentration.

Analysis of Variance↗

Morbidity and mortality in patients with coronary artery disease undergoing orthotopic liver transplantation.

Thirty-two patients with coronary artery disease who underwent liver transplantation between 1990 and 1994 were identified. Coronary artery disease was managed medically (n = 9), by angioplasty (n = 1), or surgically (n = 22) prior to liver transplantation. Two patients underwent simultaneous coronary artery bypass grafting and liver transplantation. Complete preoperative cardiac evaluation was performed in all patients. Perioperative and postoperative morbidity and mortality were retrospectively determined. Overall mortality was 50%, whereas morbidity was 81%. Follow-up was between 1 and 3 years after liver transplantation. Subgroup analysis revealed that medically managed patients had a 56% mortality and a 100% morbidity. The patient who underwent angioplasty survived without morbidity. One patient who underwent simultaneous coronary artery bypass grafting and liver transplantation died intraoperatively. The second patient survived but required pacemaker insertion and inotropic agents postoperatively. The 20 patients with prior coronary artery bypass grafting had a 50% mortality and 80% morbidity. Further, analysis by United Network for Organ Sharing functional status revealed a higher than expected mortality in all groups. The morbidity and mortality associated with liver transplantation is significantly increased in patients with coronary artery disease and is equally high in medically and surgically treated patients. By comparison, patients without coronary artery disease have a 3-year survival of 55.4% (status I) to 79.7% (status III and IV). The increased intraoperative and postoperative risk in patients with coronary artery disease undergoing liver transplantation should be considered when determining the candidacy of these patients as well as when providing informed consent.

Adult↗

Pharmacokinetics and pharmacodynamics of cisatracurium in patients with end-stage liver disease undergoing liver transplantation.

We determined the pharmacokinetics and pharmacodynamics of cisatracurium, one of the 10 isomers of atracurium, in 14 patients with end-stage liver disease undergoing liver transplantation and in 11 control patients with normal hepatic and renal function undergoing elective surgery. Blood samples were collected for 8 h after i.v. bolus administration of cisatracurium 0.1 mg kg-1 (2 x ED95). Plasma concentrations of cisatracurium and its metabolites were determined using an HPLC method with fluorescence detection. Pharmacokinetic variables were determined using non-compartmental methods. Neuromuscular block was assessed by measuring the electromyographic evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve using a Puritan-Bennett Datex (Helsinki, Finland) monitor. Pharmacodynamic modelling was completed using semi-parametric effect-compartment analysis. Volume of distribution at steady state was 195 (SD 38) ml kg-1 in liver transplant patients and 161 (23) ml kg-1 in control patients (P < 0.05), plasma clearance was 6.6 (1.1) ml kg-1 min-1 in liver transplant patients and 5.7 (0.8) ml kg-1 min-1 in control patients (P < 0.05), but elimination half-lives were similar: 24.4 (2.9) min in liver transplant patients vs 23.5 (3.5) min in control patients (ns). The time to maximum block was 2.4 (0.8) min in liver transplant patients compared with 3.3 (1.0) min in control patients (P < 0.05), but the clinical effective duration of action (time to 25% recovery) was similar: 53.5 (11.9) min in liver transplant patients compared with 46.9 (6.9) min in control patients (ns). The recovery index (25-75% recovery) was also similar in both groups: 15.4 (4.2) min in liver transplant patients and 12.8 (1.9) min in control patients (ns). After cisatracurium, peak laudanosine concentrations were 16 (5) and 21 (5) ng ml-1 in liver transplant and control patients, respectively. In summary, minor differences in the pharmacokinetics and pharmacodynamics of cisatracurium in liver transplant and control patients were not associated with any clinically significant differences in recovery profiles after a single dose of cisatracurium.

Adult↗