Charles Her

Combined epidural and general anesthesia for abdominal aortic surgery

The hypothesis that combined epidural and light general anesthesia for infrarenal abdominal aortic surgery is associated with a more stable intraoperative course and less postoperative morbidity than general anesthesia alone was tested. The authors compared intraoperative hemodynamic variables and postoperative morbidity between a group with combined epidural and general anesthesia (n = 30) and a group with general anesthesia (n = 19). Patients who had combined epidural and general anesthesia were given epidural bupivacaine intraoperatively and epidural morphine postoperatively. After cross-clamping of the aorta, cardiac index and pulmonary capillary wedge pressure did not change in the group with combined epidural and general anesthesia, whereas cardiac index decreased (mean change, 0.30 L/min/m2; P = 0.0006) and pulmonary capillary wedge pressure increased (mean change, 1 mm Hg; P = 0.007) in the group with general anesthesia. After unclamping, cardiac index increased in both groups (mean change, 0.26 L/min/m2, P = 0.002, and 0.30 L/min/m2, P = 0.001, respectively). Postoperatively, the necessity for ventilatory support and the incidence of respiratory failure were lower in the combined epidural and general anesthesia group than in the general anesthesia group (P = 0.0002 and P = 0.018, respectively). In addition, vasodilator therapy was required less frequently in the group with combined epidural and general anesthesia (P = 0.002). Duration of intensive care unit stay was shorter in the combined epidural and general anesthesia group (2.7 days v 3.8 days, P = 0.003). These data indicate that for infrarenal abdominal aortic surgery, combined epidural and general anesthesia is associated with more stable intraoperative hemodynamics and significantly less postoperative morbidity than general anesthesia alone.

Accurate assessment of right ventricular function in acute respiratory failure.

Objective:Since right ventricular ejection fraction is highly dependent on afterload, right ventricular ejection fraction may not reflect right ventricular contractile function in acute respiratory failure. Despite a severe reduction in right ventricular ejection fraction, the right ventricle may be able to generate pressure output that is sufficient enough to maintain an adequate distribution of pulmonary perfusion. We tested this hypothesis by assessing the correlation between the right ventricular ejection fraction and the right ventricular end-systolic pressure-volume relationship, and by assessing the correlations between right ventricular ejection fraction and the physiologic deadspace/tidal volume ratio and between the physiologic deadspace/tidal volume ratio and the right ventricular end-systolic pressure-volume relationship. Design:Prospective study. Setting:University hospital intensive care unit (ICU). Patients:Twenty-one patients with acute respiratory failure. Measurements and Main Results:The physiologic deadspace/tidal volume ratio was used as an index of the distribution of pulmonary perfusion. Right ventricular ejection fraction was measured by the thermodilution method. Right ventricular end-diastolic volume index was obtained from the stroke volume index divided by the right ventricular ejection fraction. Right ventricular end-systolic volume index was calculated as the difference between the right ventricular end-diastolic volume index and the stroke volume index. Pulmonary arterial dicrotic notch pressure was used as an estimate of right ventricular end-systolic pressure. Data were collected at baseline and after one or two alterations in preload to define the right ventricular end-systolic pressure-volume relationship. There was no correlation between the right ventricular ejection fraction and the slope of the right ventricular end-systolic pressure-volume relationship line. No correlation was found between the right ventricular ejection fraction and the physiologic deadspace/tidal volume ratio. There was a hyperbolic curvilinear relationship between the physiologic deadspace/tidal volume ratio and the slope of the right ventricular end-systolic pressure-volume relationship line (r2 = .82,p < .0001). When the patients were divided into two groups based on the slope of the right ventricular end-systolic pressure-volume relationship line, the physiologic deadspace/tidal volume ratio was lower in the group with a high slope of the right ventricular end-systolic pressure-volume relationship line (p < .0001). There was no difference in other hemodynamic data between the two groups. Conclusions:These data suggest that in acute respiratory failure, the right ventricular ejection fraction does not reflect right ventricular performance.(Crit Care Med 1993; 21:1665–1672)

Increased pulmonary venous resistance contributes to increased pulmonary artery diastolic-pulmonary wedge pressure gradient in acute respiratory distress syndrome.

Background:Pulmonary artery diastolic (PAD)–pulmonary wedge pressure (PWP) gradient has been shown to be increased in sepsis and acute respiratory distress syndrome (ARDS). Because pulmonary venous vasoconstriction induced by endotoxemia in sepsis or postcapillary leukocyte aggregation in ARDS or both can increase pulmonary venous resistance (Rpv), it is possible that the elevated Rpv increases PAD-PWP. The authors examined this possibility by assessing the correlation between Rpv and PAD-PWP gradient in patients with ARDS. Methods:Included were 20 patients with ARDS who required surgical procedures during general anesthesia. Rpv was calculated as the difference between mean pulmonary artery (PA) output pressure and PWP divided by cardiac index. Mean PA output pressure was computed from harmonic form of the recorded PA pressure by applying an attenuating factor to its phasic components, for which Fourier analysis was used. Total pulmonary vascular resistance (TPVR) was calculated as the difference between mean PA input pressure and PWP divided by cardiac index. To avoid the effect of PA resistance on TPVR and Rpv, the relative pulmonary venous resistance (Rpv/TPVR) was used. Results:There was a good correlation between Rpv/TPVR and PAD-PWP gradient (R2 = 0.698, P < 0.0001). When patients were classified into two groups based on PAD-PWP gradient, the Rpv/TPVR was 0.66 ± 0.06 in the group with a PAD-PWP gradient of 6 mmHg or greater and 0.46 ± 0.08 in the other group (P < 0.0001). Conclusion:A strong correlation between Rpv/TPVR and PAD-PWP gradient suggests that the increased Rpv contributes to increased PAD-PWP gradient in patients with ARDS.

Elevated Pulmonary Artery Systolic Storage Volume Associated With Redistribution Of Pulmonary Perfusion

The possibility that an increased pulmonary arterial systolic storage volume (PASSV) correlates with a significant redistribution of pulmonary perfusion was examined in 30 surgical patients. Right ventricular stroke work index (RVSWI) was used as an index of distribution of pulmonary perfusion. The systolic storage volume was calculated from the pulmonary arterial compliance and mean pulmonary arterial distending pressure. Pulmonary arteriolar pressures were computed by Fourier analysis. Pulmonary arterial compliance was derived from the pulmonary arterial time constant and pulmonary arterial resistance. There was a linear relationship between PASSV and RVSWI (r = .81, p less than .001). Also, a direct correlation was found between RVSWI and pulmonary arterial time constant (r = .45, p less than .01). When the patients were divided into three groups according to the severity of pre-existing disease, linear relationships between PASSV and RVSWI were present in all groups, and the slopes were not different among the three groups. The patients were also divided into two groups based on a storage volume fraction of stroke volume index, to evaluate the effect of other hemodynamic data on the PASSV. Comparison of the two groups revealed that pulmonary arterial pressure and pulmonary arterial compliance were significantly higher in the group with a high storage volume fraction (p = .05 and p = .01, respectively). RVSWI and time constant were also significantly different between the groups (p less than .01 and p less than .01, respectively). We conclude that the pressure work generated by the right ventricle improved the distribution of pulmonary perfusion by increasing PASSV.

Increased pulmonary venous resistance in morbidly obese patients without daytime hypoxia: clinical utility of the pulmonary artery catheter.

Background:The pulmonary artery (PA) diastolic-pulmonary capillary wedge pressure (PAD-PCWP) gradient has been shown to be increased in morbidly obese patients without daytime hypoxia. In sepsis, the increased pulmonary venous resistance (PvR) contributes to increases in PAD-PCWP gradient. In addition, the obesity-related endotoxemia is known to be involved in the pathophysiology of metabolic syndrome in obesity. Therefore, it is possible that the increased PvR contributes to increases in PAD-PCWP gradient in morbid obesity. We examined this possibility. Methods:Included were 25 obese patients without daytime hypoxia undergoing bariatric surgery under general anesthesia. PvR was calculated as the difference between mean PA output pressure and PCWP divided by cardiac index. Mean PA output pressure was computed from the harmonic form of the recorded PA pressure by applying an attenuating factor to its phasic components, for which Fourier analysis was used. Total pulmonary vascular resistance (TPVR) was calculated as the difference between mean PA pressure and PCWP divided by cardiac index. To avoid the effect of PA resistance on TPVR and PvR, the PvR/TPVR ratio was used. Results:There was a good correlation between PvR/TPVR ratio and PAD-PCWP gradient (r2 = 0.785, P < 0.0001). When patients were divided into two groups based on PAD-PCWP gradient, the PvR/TPVR ratio was 0.67 ± 0.06 (mean ± SD) in the group with a PAD-PCWP gradient of at least 6 mmHg and 0.48 ± 0.05 in the other group (P < 0.0001). Conclusions:A strong correlation between PvR/TPVR ratio and PAD-PCWP gradient suggests that the increased PvR contributes to increased PAD-PCWP gradient in obese patients without daytime hypoxia.

Assessment of right ventricular function by right ventricular systolic time intervals in acute respiratory failure.

OBJECTIVE Whether right ventricular systolic time intervals accurately reflect right ventricular function in patients with acute respiratory failure was determined by assessing the correlation between right ventricular systolic time intervals and the right ventricular end-systolic pressure-volume relationship. DESIGN A prospective study. SETTING A surgical intensive care unit in a university hospital. PATIENTS Twenty patients with acute respiratory failure. MEASUREMENTS AND MAIN RESULTS Right ventricular systolic time intervals were determined by the simultaneous graphic display of the electrocardiogram, the phonocardiogram, and the pulmonary artery pressure curve and were expressed as a ratio of the pre-ejection period/right ventricular ejection time. The total electromechanical systole was measured from the onset of the electrocardiographic wave complex to the pulmonic component of the second heart sound. Right ventricular ejection time was measured from the rapid upstroke of the pulmonary artery pressure curve to the dicrotic notch. Right ventricular ejection fraction, from which right ventricular end-systolic volume was derived, was measured by the thermodilution technique. Pulmonary artery dicrotic notch pressure was used as an estimate of right ventricular end-systolic pressure. Data were collected at the baseline and after one or two alterations in preload, to define the right ventricular end-systolic pressure-volume relationship line. There was an inverse correlation between the pre-ejection period/right ventricular ejection time ratio and the slope of the right ventricular end-systolic pressure-volume relationship line (r2 = .67; p < .0001). When patients were divided into two groups, based on the pre-ejection period/right ventricular ejection time ratio, the slope of the right ventricular end-systolic pressure-volume relationship line was lower in the group with a high pre-ejection period/right ventricular ejection time ratio (p < .0001). No difference in other hemodynamic data, between the two groups, was noted. CONCLUSIONS These data suggest that right ventricular systolic time intervals reflect right ventricular performance accurately in patients with acute respiratory failure.

Acetaminophen-induced, Not Desflurane-induced, Hepatotoxicity

To the Editor:—I believe that the case of hepatotoxicity after desflurane anesthesia in a 15-month-old child with Mobius syndrome after previous exposure to isoflurane, reported by Drs. Côté and Bouchard, is not a case of desflurane-induced but acetaminophen-induced hepatotoxicity. Drs. Côté and Bouchard ignored that liver enzyme levels were too high for desflurane-induced hepatotoxicity, that the serum level of acetaminophen on the second postoperative day after multiple doses was high enough to induce hepatotoxicity, and that omeprazole is an inducer of the cytochrome P-450 enzymes (CYPs) CYP 1A2 and CYP 3A4, which increase oxidative metabolism of acetaminophen. They also ignored that cisapride increases the bioavailability of acetaminophen by inhibiting its glucuronidation in humans. Cases of hepatotoxicity after isoflurane, enflurane, and desflurane anesthesia in the previous reports provided by Drs. Côté and Bouchard for references had increased liver enzymes, such as alanine aminotransferase and aspartate aminotransferase, and bilirubin, but none of the cases had a serum level of alanine aminotransferase or aspartate aminotransferase higher than 3,000 U/l, except one case in which the sample was taken after cardiac arrest. The increased bilirubin level and jaundice were prominent in those cases. On the contrary, acute acetaminophen hepatotoxicity is characterized by marked increases in the aminotransferases, usually more than 3,000 U/l, the bilirubin level is somewhat inconsistent in the correlation of degree of its increase to hepatic damage, and the onset of jaundice is delayed. Therefore, the clinical feature seems to be acetaminophen toxicity. The half-life of acetaminophen in healthy volunteers given high therapeutic doses is approximately 2 h. The half-life of acetaminophen in patients with hepatotoxicity is in excess of 4 h. Single plasma levels of acetaminophen are not as reliable as plasma half-life. However, single plasma levels may be used with a Rumack–Matthew acetaminophen nomogram (fig. 1) as a rough prognostic guide. In case of multiple doses of acetaminophen, the number of days from first ingestion for overdose and number of hours from last administration for therapeutic use (this information was not provided in the case report by Drs. Côté and Bouchard) should be taken into consideration when a single plasma level of acetaminophen is evaluated for possible toxicity. In a child who developed severe hepatotoxicity necessitating liver transplantation, the plasma level of acetaminophen was reported to be 66 M on admission to the emergency department 3 days after first ingestion of multiple overdoses of acetaminophen, which had been taken for 2 days. In another pediatric patient, who developed hepatotoxicity with stage 2 encephalopathy, the plasma level of acetaminophen was 152 M on admission 2 days after first ingestion of multiple overdoses of acetaminophen, which had been taken for 1 day. In the case report by Drs. Côté and Bouchard, the plasma level of acetaminophen of 210 M on the second postoperative day after multiple therapeutic doses was very high and high enough to induce hepatotoxicity, and their statement that “the acetaminophen level was in the therapeutic range” was not correct. Acetaminophen is excreted rapidly, even in patients with liver damage. If the plasma acetaminophen level is maintained in the therapeutic range (as Drs. Côté and Bouchard reported) of 210 M for more than 18 h (as shown in fig. 1), almost all patients will develop hepatotoxicity. For acetaminophen, there is no such thing as a therapeutic range of plasma level. More than 90% of acetaminophen in the body is metabolized by way of conjugation, two thirds through glucuronidation and one third through sulfation. Approximately 5–9% undergoes oxidative conversion by CYPs (CYP1A2, CYP2E1, CYP3A4) to the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). CYP2E1 is the major source of NAPQI, with less contribution from CYP1A2 and CYP3A4. NAPQI is rapidly metabolized by conjugation with glutathione, forming a nontoxic acetaminophen–glutathione conjugate. The degree of hepatic toxicity correlates with the activity of the metabolic pathway and glutathione availability. Overdoses of acetaminophen lead to the saturation of the glucuronidation and sulfation pathways, shunting more acetaminophen into the CYP system. The increased metabolism of acetaminophen by the CYP system increases the production of NAPQI. Glutathione stores within the liver are limited and will be depleted in an attempt to metabolize the increased NAPQI, and then NAPQI will accumulate, leading to hepatotoxicity. Cisapride has been shown to inhibit conjugation of acetaminophen via glucuronidation without affecting conjugation via sulfation. The coadministration of acetaminophen with cisapride can reduce acetaminophen glucuronide conjugate concentration and increase the availability of acetaminophen into the CYP system. Therefore, cisapride may be able to lead hepatotoxicity at therapeutic doses of acetaminophen. In addition, there is evidence that induction of CYPs other than CYP2E1, such as CYP1A2 and CYP3A4, can increase oxidative metabolism of acetaminophen, leading to hepatotoxicity at therapeutic dosages. Although omeprazole has been shown to be a strong inducer of CYP1A2 and a weak inducer of CYP3A4, omeprazole does not increase oxidative metabolism at therapeutic doses of acetaminophen. However, at overdoses of acetaminophen, the inducers could augment the hepatotoxic effect. It is most likely that the combination of cisapride and omeprazole in the case reported by Drs. Côté and Bouchard contributed to decreased conjugation via glucuronidation and increased oxidative metabolism of acetaminophen, leading to hepatotoxicity in the presence of acetaminophen overdose. The absence of any problem with the liver after an eye procedure during total intravenous anesthesia 7 months later does not support the notion that the previous event was desflurane-induced hepatotoxicity. Possible explanations for the absence of hepatotoxicity after the eye The above letter was sent to the authors of the referenced report. The authors did not feel that a response was required.—James C. Eisenach, M.D., Editor-in-Chief. Fig. 1. Rumack–Matthew acetaminophen nomogram. The nomogram shows the relation between plasma acetaminophen concentration, time after drug ingestion, and the risk for hepatotoxicity. From Larson; adapted with permission.