Shushma Aggarwal

Postreperfusion syndrome: Hypotension after reperfusion of the transplanted liver

Sixty-nine patients undergoing liver transplantation were evaluated to elucidate the relationship between hypotension and physiological changes seen on reperfusion of the grafted liver. Measured variables included hemodynamic profiles, core temperature, serum potassium, ionized calcium levels, arterial blood-gas tensions, and acid-base state. Measurements were taken 60 minutes after skin incision (baseline), 5 minutes before reperfusion, and 30 seconds and 5 minutes after reperfusion. On the basis of changes in mean arterial pressure (MAP) patients were divided in two groups. Group 1 (n = 49) maintained MAP greater than 70% and group 2 (n = 20) had MAP less than 70% of the baseline value for at least 1 minute within 5 minutes after reperfusion. On reperfusion, changes common to both groups were 27% increase in cardiac filling pressures, 23% base deficit, and 30% serum potassium level and a decrease of 16% in cardiac output and 9% in temperature. Compared with group 1, group 2 had greater decrease in systemic vascular resistance (SVR) (1097 +/- 868 and 741 +/- 399 dyn.s-1. cm-5, respectively, P < .05) and higher potassium level (4.5 +/- 0.8 and 5.3 +/- 0.8 mmol/L, P < .05). Collectively in both groups, there was no correlation between MAP and physiological variables; however, there was a poor correlation with SVR (r = .32, P < .01). Reperfusion hypotension seen in group 2 patients correlated only with a decrease in systemic vascular resistance (r = .5, P < .05). Acute hyperkalemia, hypothermia, and acidosis do not appear to be major causes of reperfusion hypotension.

Noninvasive monitoring of cerebral perfusion pressure in patients with acute liver failure using transcranial doppler ultrasonography

Elevated intracranial pressure (ICP) leads to loss of cerebral perfusion, cerebral herniation, and irreversible brain damage in patients with acute liver failure (ALF). Conventional techniques for monitoring ICP can be complicated by hemorrhage and infection. Transcranial doppler ultrasonography (TCD) is a noninvasive device which can continuously measure cerebral blood flow velocity, producing a velocity‐time waveform that indirectly monitors changes in cerebral hemodynamics, including ICP. The primary goal of this study was to determine whether TCD waveform features could be used to differentiate ALF patients with respect to ICP or, equally important, cerebral perfusion pressure (CPP) levels. A retrospective study of 16 ALF subjects with simultaneous TCD, ICP, and CPP measurements yielded a total of 209 coupled ICP‐CPP‐TCD observations. The TCD waveforms were digitally scanned and seven points corresponding to a simplified linear waveform were identified. TCD waveform features including velocity, pulsatility index, resistive index, fraction of the cycle in systole, slopes, and angles associated with changes in the slope in each region, were calculated from the simplified waveform data. Paired ICP‐TCD observations were divided into three groups (ICP < 20 mmHg, n = 102; 20 ≤ ICP < 30 mmHg, n = 74; and ICP ≥ 30 mmHg, n = 33). Paired CPP‐TCD observations were also divided into three groups (CPP ≥ 80 mmHg, n = 42; 80 > CPP ≥ 60 mmHg, n = 111; and CPP < 60 mmHg, n = 56). Stepwise linear discriminant analysis was used to identify TCD waveform features that discriminate between ICP groups and CPP groups. Four primary features were found to discriminate between ICP groups: the blood velocity at the start of the Windkessel effect, the slope of the Windkessel upstroke, the angle between the end systolic downstroke and start diastolic upstroke, and the fraction of time spent in systole. Likewise, 4 features were found to discriminate between the CPP groups: the slope of the Windkessel upstroke, the slope of the Windkessel downstroke, the slope of the diastolic downstroke, and the angle between the end systolic downstroke and start diastolic upstroke. The TCD waveform captures the cerebral hemodynamic state and can be used to predict dynamic changes in ICP or CPP in patients with ALF. The mean TCD waveforms for corresponding, correctly classified ICP and CPP groups are remarkably similar. However, this approach to predicting intracranial hypertension and CPP needs to be further refined and developed before clinical application is feasible. Liver Transpl 14:1048–1057, 2008.

Cerebral hemodynamic and metabolic profiles in fulminant hepatic failure: Relationship to outcome

The purpose of this retrospective study was to examine the potential role of cerebral hemodynamic and metabolic factors in the outcome of patients with fulminant hepatic failure (FHF). Based on the literature, a hypothetical model was proposed in which physiologic changes progress sequentially in five phases, as defined by intracranial pressure (ICP) and cerebral blood flow (CBF) measurements. Seventy‐six cerebral physiologic profiles were obtained in 26 patients (2 to 5 studies each) within 6 days of FHF diagnosis. ICP was continuously measured by an extradural fiber optic monitor. Global CBF estimates were obtained by xenon clearance techniques. Jugular venous and peripheral artery catheters permitted calculation of cerebral arteriovenous oxygen differences (AVDO2), from which cerebral metabolic rate for oxygen (CMRO2) was derived. A depressed CMRO2 was found in all patients. There was no evidence of cerebral ischemia as indicated by elevated AVDO2s. Instead, over 65% of the patients revealed cerebral hyperemia. Eight of the 26 patients underwent orthotopic liver transplantation—all recovered neurologically, including 6 with elevated ICPs. Of the 18 patients receiving medical treatment only, all 7 with increased ICP died in contrast to 9 survivors whose ICP remained normal (P < 0.004). Hyperemia, per se, was not related to outcome, although it occurred more frequently at the time of ICP elevations. Six patients were studied during brain death. All 6 revealed malignant intracranial hypertension, preceded by hyperemia. In conclusion, the above findings are consistent with the hypothetical model proposed. Prospective longitudinal studies are recommended to determine the precise evolution of the pathophysiologic changes. (Liver Transpl 2005;11:1353–1360.)

Pharmacokinetics and pharmacodynamics of doxacurium in normal patients and in those with hepatic or renal failure.

&NA; We determined the pharmacokinetics and duration of action of a bolus dose of doxacurium (15 μg/kg) in 27 patients anesthetized with isoflurane and nitrous oxide. Nine patients had normal renal and liver functions and were undergoing a variety of surgical procedures, nine were undergoing cadaveric kidney transplantation because of end‐stage renal disease, and nine were undergoing cadaveric liver transplantation because of end‐stage hepatocellular disease. Plasma concentrations of doxacurium were measured for 6 h after administration using a sensitive and specific capillary gas chromatographic assay. Plasma concentration versus time data were analyzed by a noncompartmental method based on statistical moments. Neuromuscular blockade was assessed by measuring the electromyographic evoked response of the adductor pollicis muscle to train‐of‐four stimulation of the ulnar nerve. The degree of neuromuscular blockade after doxacurium administration was described as the percent of control of the first train‐of‐four response. The pharmacokinetic variables were (normal vs hepatic failure vs renal failure, respectively): volume of distribution at steady state (220 ± 110 vs 290 ± 60 vs 270 ± 130 mL/kg [mean ± SD]), plasma clearance (2.7 ± 1.6 vs 2.3 ± 0.4 vs 1.2 ± 0.7 mL·kg−1·min−1), mean residence time (95.2 ± 57 vs 129.4 ± 30 vs 270 ± 210 min), and elimination half‐life (99 ± 54 vs 115 ± 31 vs 221 ± 156 min). Plasma clearance and mean residence time differed significantly between patients with renal failure and control patients. There was no significant difference in the onset times or in clinical effective duration, although the clinical duration tended to be longer and more variable in the patients with renal failure. This unpredictable response and the possibility of prolonged blockade should be borne in mind if doxacurium is to be used in patients with renal failure.

Regional Cerebral Blood Flow and CO2 Reactivity in Fulminant Hepatic Failure

Alterations in cerebral hemodynamics are postulated to contribute to brain herniation, a major cause of death in patients with severe hepatic encephalopathy due to fulminant hepatic failure (FHF). In an effort to identify these changes in cerebral hemodynamics, regional and global cerebral blood flow (CBF) and CO2 reactivity were measured using stable xenon-enhanced computed tomography (Xe/CT) in 24 patients within 72 h of onset of severe hepatic encephalopathy. Regional variations in CBF, most notably, a relative decrease in CBF in the anterior circulation and an increase in CBF in the posterior circulation were found. CBF was significantly lower in FHF patients compared with controls, however, these values are well out of the established ischemic range. FHF patients also showed significant impairment in CBF response to hypoventilation, while the CBF response to hyperventilation remained intact. This study suggests that FHF patients demonstrate early changes in both CBF patterns and CO2 reactivity. The relatively “normal” CBF values obtained in FHF patients in severe hepatic encephalopathy coupled with the lack of vasodilatation to hypoventilation suggest a state of uncoupled CBF and metabolism or “luxury perfusion” that could theoretically contribute to vasogenic edema, brain swelling, and cerebral herniation.

Monitoring Preload During Liver Transplantation

Liver transplantation is associated with major shifts incentral blood volume; therefore, monitoring preload is es-sential. Filling pressures (central venous pressure or pul-monary artery occlusion pressure) do not reflect preload[right ventricular end-diastolic volume (RVEDV) or leftventricular end-diastolic volume (LVEDV)] well becausethese pressures are affected not just by preload but alsoby changes in compliance of the heart. These compliancechanges can be quite significant because of the changesin chest volume that are the result of surgical retractionand variable pressure on the diaphragm. Then, what arethe alternative methods of preload monitoring in the op-erating room? There are only two: thermodilution deter-mination of RVEDV and transesophageal echocardio-graphic estimation of RVEDV and LVEDV. Each of thesetechniques has advantages and disadvantages.The clinical determination of the right ventricularejection fraction (RVEF) and RVEDV became possible inthe early 1980s when American Edwards Laboratoriesmarketed a pulmonary artery catheter with a fast-re-sponse thermistor and an accompanying computer.That technology was based on intermittent injection ofa cold solution as a dye, and the principle of conserva-tion of energy allowed the calculation of RVEF and rightventricular volumes.

Cirrhosis is not a contraindication to laparoscopic cholecystectomy: results and practical recommendations

BACKGROUND Gallstones appear more frequently in patients with cirrhosis and open cholecystectomy in this patient population is associated with higher morbidity and mortality. The aim of the present study was to evaluate experience with laparoscopic cholecystectomy in patients with cirrhosis and to provide recommendations for management. METHODS Retrospective review of laparoscopic cholecystectomy in patients with cirrhosis from March 1999 to May 2008 was performed. Peri-operative characteristics and subgroup analysis were performed in patients with Child-Pughs classes A, B and C cirrhosis. RESULTS A total of 68 patients were reviewed in this study. In all, 69% of the patients were Childs class A. The most common indication for cholecystectomy was chronic/symptomatic cholelithiasis (68%). Compared with patients with Childs class B and C, laparoscopic cholecystectomy in patients with Childs class A was associated with significantly decreased operative time (P= 0.01), blood loss (P= 0.001), conversion to open cholecystectomy (P= 0.001) and length of hospital stay (P= 0.001). CONCLUSIONS Laparoscopic cholecystectomy in patients with cirrhosis is feasible with no mortality and low morbidity, especially in patients with Childs class A cirrhosis.

Analysis of vascular access in intestinal transplant recipients using the Miami classification from the VIIIth International Small Bowel Transplant Symposium.

Background. Loss of vascular access in patients with intestinal failure is considered an indication for intestinal transplantation. Such patients often have one or more occluded vein sites. Venous access could be classified according to the number of occluded vessels, to facilitate pre- and postoperative management. Methods. At the VIIIth International Small Bowel Transplant Symposium in September 2003, a new classification of vascular access in patients who were candidates for bowel transplant was proposed. The classification was then applied to stratify all patients that underwent intestinal transplantation at the University of Miami between 1998 and 2003. Data were collected on Doppler ultrasonography, angiography, and vein angioplasty in such patients. Results. A total of 106 cases in 91 patients were included in the study. Based on Doppler ultrasound results, 51.9% of patients fell into class I (no thrombosed vessels), 21.7% were in class II (one occluded vessel, or positive risk factors for thrombosis), 24.5% were in class III (multiple thrombosed vessels), and 1.9% were in class IV (all vessels thrombosed). Fifteen percent of the patients required preoperative angiography to better evaluate venous access. Most of the patients that required angiography were in class III or IV, and 53.3% of patients requiring angiography needed additional venous angioplasty to achieve access. Conclusions. All patients that are referred for intestinal transplantation should undergo preliminary mapping of their venous access by Doppler ultrasound and then be assigned to a vascular access class. Those patients with multiple thrombosed vessels (class III and above) should be strongly considered for additional angiographic evaluation.

Simulation: a teaching tool for liver transplantation anesthesiology

Aggarwal S, Bane BC, Boucek CD, Planinsic RM, Lutz JW, Metro DG. Simulation: a teaching tool for liver transplantation anesthesiology.

Central venous thrombosis and perioperative vascular access in adult intestinal transplantation

BACKGROUND Venous access is crucial in intestinal transplantation, but a thrombosed venous system may prevent the use of central veins of the upper body. The incidence of venous thrombosis and the necessity to perform alternative vascular access (AVA) in intestinal transplant recipients have not been fully investigated. METHODS Records of adult patients who underwent intestinal transplantation between January 1, 2001, and December 31, 2009, were reviewed. Contrast venography was performed as pre-transplantation screening. Vascular accesses at the transplantation were categorized as I (percutaneous line via the upper body veins), II (percutaneous line via the lower body veins), and III (vascular accesses secured surgically, with interventional radiology, or using non-venous sites). Categories II and III were defined as AVA. Risk factors for central venous thrombosis and those for requiring AVA were analysed, respectively. RESULTS Among 173 patients, central venous obstruction or stenosis (<50% of normal diameter) was found in 82% (141 patients). AVA was required in 4.6% (eight patients: four in each category II and III). Large-bore infusion lines were placed via the femoral arteries in all category III patients without complications. Existing inferior vena cava filter and hypercoagulable states were identified as the risk factors for the use of AVA, but not for central venous thrombosis. Outcomes of patients who underwent AVA were similar to those of patients without AVA. CONCLUSIONS The majority of adult patients undergoing intestinal transplantation had at least one central venous stenosis or obstruction. The recipient outcomes were comparable when either standard vascular access or AVA was used for transplantation.