Kyeo-Woon Jung

Effect of ventriculo-arterial coupling on transplant outcomes in cirrhotics: Analysis of pressure-volume curve relations

BACKGROUND & AIMS Ventriculo-arterial coupling (VAC) reflects the interaction between ventricular performance and effective arterial load. Current criteria for cirrhotic cardiomyopathy focus only on cardiac function without addressing the effect of hyperdynamic, low-resistance circulation. We investigated alterations in VAC in cirrhotic patients and their associations with post-liver transplant all-cause mortality. METHODS In this single institution cohort study, cirrhotic patients who underwent liver transplantation (LT) (n=914) were retrospectively compared with healthy matched controls using noninvasively measured end-systolic ventricular elastance (Ees), arterial elastance (Ea), and VAC (Ea/Ees). All-cause mortality based on VAC values were investigated using a Cox hazard model with the inverse probability treatment weighting (IPTW) of propensity score. RESULTS Cirrhotic patients had significantly lower Ees, Ea and VAC values than controls. Over a median of 30months, 96 patients died after LT. In patients with a high model for end-stage liver disease score (⩾25), VAC of >0.61 (highest tertile) had poorer survival outcomes than patients with VAC of ⩽0.50 (lowest tertile) (66.0% vs. 91.8%; Log-rank p=0.001), and was independently associated with risk of mortality (hazard ratio, 2.44; 95% CI, 1.10-5.39; p=0.028) compared with VAC of ⩽0.61 after IPTW adjustment. CONCLUSIONS In cirrhotic patients, ventricular elastance and VAC values are lower than those in controls. However, in advanced cirrhotic patients, an increase in VAC value is associated with all-cause mortality after LT, suggesting that this non-invasive estimation of ventriculo-arterial uncoupling is an additional novel prognosticator in cirrhotic cardiovascular disorders. LAY SUMMARY In cirrhotic patients, cardiac dysfunction is latent and only manifests under stressful conditions because of arterial vasodilation. In this study, based on the pressure-volume curve of cardiac function, we investigated characteristics of the ventricular-arterial coupling in cirrhotic patients and further found that disparities in the ventriculo-arterial relationship are associated with graft failure and all-cause mortality after liver transplantation.

Predictive performance of the modified Marsh and Schnider models for propofol in underweight patients undergoing general anaesthesia using target-controlled infusion

Background : In our preliminary study, the modified Marsh (M-Marsh) model caused an inadvertent underdosing of propofol in underweight patients. However, the predictive performance of the M-Marsh and Schnider models incorporated in commercially available target-controlled infusion (TCI) pumps was not evaluated in underweight patients. Methods : Thirty underweight patients undergoing elective surgery were randomly allocated to receive propofol via TCI using the M-Marsh or Schnider models. The target effect-site concentrations (Ces) of propofol were, in order, 2.5, 3, 4, 5, 6 and 2 μg ml -1 . Arterial blood samples were obtained at least 7 min after achieving each pseudo-steady-state. Results A total of 172 plasma samples were used to determine the predictive performance of both models. The pooled median (95% confidence interval) biases and inaccuracies at a target Ce ≤ 3 μg ml -1 were -22.6 (-28.8 to -12.6) and 31.9 (24.8-36.8) for the M-Marsh model and 9.0 (1.7-16.4) and 28.5 (21.7-32.8) for the Schnider model, respectively. These values at Ce ≥ 4 μg ml -1 were -9.6 (-16.0 to -6.0) and 24.7 (21.1-27.9) for the M-Marsh model and 19.8 (12.9-25.7) and 36.2 (31.4-39.7) for the Schnider model, respectively. Conclusions The pooled biases and inaccuracies of both models were clinically acceptable. However, the M-Marsh and Schnider models consistently produced negatively and positively biased predictions, respectively, in underweight patients. In particular, the M-Marsh model showed greater inaccuracy at target Ce   ≤   3 μg ml -1 and the Schnider model showed greater inaccuracy at target Ce ≥ 4 μg ml -1 . Therefore, it is necessary to develop a new pharmacokinetic model for propofol in underweight patients. Clinical trial registration KCT0001502.

Comparison of the analgesic effect of patient‐controlled oxycodone and fentanyl for pain management in patients undergoing colorectal surgery

Oxycodone is a μ‐opioid receptor agonist and is generally indicated for the relief of moderate to severe pain. The aim of this study was to compare the analgesic efficacy of patient‐controlled oxycodone and fentanyl for postoperative pain in patients undergoing colorectal surgery. Patients scheduled to undergo elective colorectal surgery (n=82) were allocated to receive oxycodone (n=41, concentration of 1 mg/mL) or fentanyl (n=41, concentration of 15 μg/mL) for postoperative pain management. After the operation, pain using a numerical rating scale (NRS), delivery to demand ratio, infused dose of patient‐controlled analgesia (PCA), side effects, and sedation levels were evaluated. Median (25%–75%) cumulative PCA dose of oxycodone group at 48 hours (66.9, 58.4–83.7 mL) was significantly less than that of fentanyl group (80.0, 63.4–103.3 mL, P=.037). Six hours after surgery, the mean (SD) NRS scores of the oxycodone and fentanyl groups were 6.2 (2.4) and 6.8 (1.9), respectively (P=.216). The mean equianalgesic potency ratio of oxycodone to fentanyl was 55:1. The groups did not differ in postoperative nausea, vomiting, and level of sedation. Patient‐controlled oxycodone provides similar effects for pain relief compared to patient‐controlled fentanyl in spite of less cumulative PCA dose. Based on these results, oxycodone can be a useful alternative to fentanyl for PCA in patients after colorectal surgery.

The comparison of predictive performance in bispectral index prediction during target effect-site controlled infusion of propofol using different blood effect-site equilibration rate constants in the same pharmacokinetic model.

Background Blood-brain equilibration rate constant (ke0) is derived from either pharmacokinetic and pharmacodynamic modeling (ke0_model) or a model-independent observed time to peak effect (ke0_tpeak). Performance in bispectral index (BIS) prediction was compared between ke0_model and ke0_tpeak for microemulsion or long chain triglyceride (LCT) propofol. Methods Time to peak effect (tpeak, time to a maximally reduced BIS value) of microemulsion propofol after an intravenous bolus (1 mg/kg) was measured in 100 patients (group Amicro). An observed tpeak of 1.6 min for LCT propofol was obtained from an earlier study. Another 40 patients received a target controlled infusions of microemulsion propofol (ke0_model = 0.187/min, group Bmicro = 20) or LCT propofol (ke0_model = 0.26/min, group BLCT = 20) and remifentanil. The ke0_tpeaks in group Bmicro and BLCT were calculated using the observed tpeak value obtained from group Amicro and 1.6 min, respectively. Effect-site concentrations of propofol were recalculated using the amounts of propofol infused over time and ke0_tpeaks. Predicted BIS values calculated by sigmoid Emax equations with ke0_model and ke0_tpeak were compared with observed BIS values during induction and emergence for both formulations of propofol. Results Observed tpeak of microemulsion propofol was 1.68 min. The median performance errors of BIS in group Bmicro were -1.83% (-24.8 to 18.9, ke0_model) and -2.42% (-26.1 to 36.2, ke0_tpeak), while 8.01% (-20.5 to 30.1, ke0_model) and 7.37% (-27.0 to 49.1, ke0_tpeak) in group BLCT. The median absolute performance errors of BIS in group Bmicro were 11.87% (2.2-31.1ke0_model) and 14.38% (-0.6 to 44.6, ke0_tpeak), while 17.31% (5.54-36.0, ke0_model) and 18.28% (-0.1 to 56.0, ke0_tpeak) in group BLCT. Conclusions The ke0_model showed better performance in BIS prediction than the ke0_tpeak.

Prevalent metabolic derangement and severe thrombocytopenia in ABO-incompatible liver recipients with pre-transplant plasma exchange

Desensitisation with therapeutic plasma exchange (TPE) is essential for ABO-incompatible (ABO-I) liver transplants (LTs). However, excessive citrate load and coagulation disturbances after TPE have been poorly studied, in particular in cirrhotic patients with hypocapnic alkalosis, metabolic compensation and electrolyte imbalances. We retrospectively evaluated 1123 consecutive LT recipients (923 ABO-compatible [ABO-C], 200 ABO-I) from November 2008 to May 2015. TPE was generally performed a day before LT and blood sampling was performed before anaesthesia induction. We performed propensity score matching (PSM) and inverse probability treatment weighting (IPTW) analyses. In 199 PSM pairs, metabolic alkalosis was prevalent in ABO-I LT recipients (expectedly due to citrate conversion) with higher pH ≥ 7.50 (IPTW-adjusted odds ratio [aOR] = 2.23) than in ABO-C LT recipients. With increasing cirrhosis severity, the arterial pH and bicarbonate levels showed dose-dependent relationships, whereas mild hypoxaemia was more prevalent in ABO-I LT recipients. ABO-I LT recipients exhibited worsened hypokalaemia ≤3.0 mmol/l (17.6%, aOR = 1.44), hypomagnesaemia ≤1.7 mg/dl (27.6%, aOR = 3.43) and thrombocytopenia <30,000/µl (19.1%, aOR = 2.26) confirmed by lower maximal clot firmness (P = 0.001) in rotational thromboelastometry (EXTEM), which necessitated platelet transfusions. Preoperative identification of these change may prevent worsening of severe electrolyte disturbances and thrombocytopenia for optimal LT anaesthesia.