Deok Man Hong

Does remote ischaemic preconditioning with postconditioning improve clinical outcomes of patients undergoing cardiac surgery? Remote Ischaemic Preconditioning with Postconditioning Outcome Trial

AIMS The aim of this study was to evaluate whether remote ischaemic preconditioning (RIPC) combined with remote ischaemic postconditioning (RIPostC) improves the clinical outcomes of patients undergoing cardiac surgery. METHODS AND RESULTS From June 2009 to November 2010, 1280 patients who underwent elective cardiac surgery were randomized into the RIPC with RIPostC group or the control group in the morning of the surgery. In the RIPC with RIPostC group, four cycles of 5-min ischaemia and 5-min reperfusion were administered twice to the upper limb-before cardiopulmonary bypass (CPB) or coronary anastomoses for RIPC and after CPB or coronary anastomoses for RIPostC. The primary endpoint was the composite of major adverse outcomes, including death, myocardial infarction, arrhythmia, stroke, coma, renal failure or dysfunction, respiratory failure, cardiogenic shock, gastrointestinal complication, and multiorgan failure. Remote ischaemic preconditioning with RIPostC did not reduce the composite outcome compared with the control group (38.0 vs. 38.1%, respectively; P = 0.998) and there was no difference in each major adverse outcome. The intensive care unit and hospital stays were not different between the two groups. However, in the off-pump coronary artery bypass surgery subgroup, multivariate logistic regression analysis revealed that RIPC with RIPostC was related to increased composite outcome (odds ratio: 1.54; 95% confidence interval: 1.02-2.30; P = 0.038). CONCLUSION Remote ischaemic preconditioning with RIPostC by transient upper limb ischaemia did not improve clinical outcome in patients who underwent cardiac surgery.

Pulse pressure variation as a predictor of fluid responsiveness during one-lung ventilation for lung surgery using thoracotomy: randomised controlled study.

Background and objective Pulse pressure variation (PPV) is increasingly advocated as a predictor of fluid responsiveness in patients receiving mechanical ventilation. However, the ability of PPV has never been studied during one-lung ventilation (OLV). Therefore, we evaluated the value of PPV to predict fluid responsiveness in patients receiving conventional and protective OLV using receiver operating characteristic (ROC) analysis, respectively. Methods Forty-nine patients undergoing lung surgery requiring OLV were enrolled in this study. Patients were randomised either to group P [patients receiving protective OLV with tidal volume 6 ml kg−1, inspired oxygen fraction (FIO2) of 0.5 and positive end-expiratory pressure (PEEP) of 5 cmH2O) or group C (patients receiving conventional OLV with tidal volume of 10 ml kg−1, FIO2 of 1.0 and no PEEP). Following OLV, PPV and cardiac output were measured before and 12 min after fluid loading (7 ml kg−1 hydroxyethyl starch 6%). Patients whose cardiac indices increased by at least 15% to fluid loading were defined as the responders. Results The areas under ROC curve for PPV were 0.857 (P = 0.006) in group P and 0.524 (P = 0.839) in group C, respectively. The optimal threshold value given by ROC analysis for PPV was 5.8% in group P. Conclusions PPV could predict fluid responsiveness only during protective OLV, but not conventional OLV. PPV would be helpful for fluid management in patients receiving protective OLV for lung surgery using thoracotomy.

Effect of palonosetron on the QTc interval in patients undergoing sevoflurane anaesthesia

BACKGROUND Palonosetron is a recently introduced 5-HT3 receptor antagonist for postoperative nausea and vomiting. Detailed standardized evaluation of corrected QT (QTc) interval change by palonosetron under sevoflurane anaesthesia is lacking. We evaluated QTc intervals in patients who are undergoing surgery with sevoflurane anaesthesia and receive palonosetron. METHODS Our study included 100 patients who were undergoing elective surgery under sevoflurane anaesthesia. The patients were randomly assigned to two groups: those who received an i.v. injection of palonosetron 0.075 mg immediately before induction of anaesthesia (pre-surgery group, n=50) and those who received it after surgery in the recovery room (post-surgery group, n=50). QTc intervals were measured before operation, intraoperatively (baseline, immediately after tracheal intubation, and at 2, 10, 15, 30, 60, and 90 min after administration of palonosetron or placebo), and after operation (before and at 3, and 10 min after administration of palonosetron or placebo). QTc intervals were calculated using Fridericias, Bazetts, or Hodges formulas. RESULTS The perioperative QTc intervals were significantly increased from the baseline values, but were not affected by the pre- or post-surgical timing of palonosetron administration. CONCLUSIONS There was no significant difference in the QTc intervals during the perioperative period, whether 0.075 mg of palonosetron is administered before or after sevoflurane anaesthesia. Palonosetron may be safe in terms of QTc intervals during sevoflurane anaesthesia. Clinical trial registration ClinicalTrials.gov: NCT01650961.

Influence of high-dose intraoperative remifentanil with intravenous ibuprofen on postoperative morphine consumption in patients undergoing pancreaticoduodenectomy: a randomized trial.

STUDY OBJECTIVE High-dose remifentanil during surgery paradoxically increases postoperative pain intensity and morphine consumption. Cyclooxygenase inhibitors decrease prostaglandin synthesis, thereby antagonizing N-methyl-d-aspartate receptor activation, and may reduce hyperalgesia. This study was performed to evaluate whether postoperative morphine consumption increased following intraoperative continuous remifentanil infusion and whether this could be prevented by intravenous ibuprofen pretreatment. DESIGN A randomized controlled study. SETTING Single university hospital, study period from September 2014 to March 2015. PATIENTS One hundred and twenty patients undergoing pancreaticoduodenectomy. INTERVENTIONS After induction of anesthesia, patients received remifentanil target-controlled infusion (effect site concentration of 4 ng/mL or 1 ng/mL) with or without intravenous ibuprofen (800 mg). MEASUREMENTS Postoperative cumulative total morphine consumption and pain intensity were assessed. MAIN RESULTS Intraoperative remifentanil use in patients receiving high-dose remifentanil was more than 3-fold higher than that in patients receiving low-dose remifentanil (2666.8 ± 858.4 vs 872.0 ± 233.3 μg, respectively; P< .001). However, cumulative total morphine consumption at postoperative 1, 3, 6, 12, 24, and 48 hours did not differ among the groups. There were no differences among the groups in the self-administered analgesic dose by the patients using a controlled analgesia device, number of self-administration attempts, numerical rating scale for pain, or analgesic side effects. CONCLUSIONS We found no influence on postoperative pain after high-dose remifentanil in patients undergoing pancreaticoduodenectomy. Addition of intravenous ibuprofen did not reduce postoperative morphine consumption or pain intensity.

Microvascular reactivity and clinical outcomes in cardiac surgery

IntroductionMicrovascular reactivity is decreased in patients with septic shock; this is associated with worse clinical outcomes. The objectives of the present study were to investigate microvascular reactivity in cardiac surgery patients and to assess any association with clinical outcomes.MethodsWe retrospectively analyzed a prospectively collected registry. In total, 254 consecutive adult patients undergoing cardiac and thoracic aortic surgeries from January 2013 through May 2014 were analyzed. We performed a vascular occlusion test (VOT) by using near-infrared spectroscopy to measure microvascular reactivity. VOT was performed three times per patient: prior to the induction of anesthesia, at the end of surgery, and on postoperative day 1. The primary endpoint was a composite of major adverse complications, including death, myocardial infarction, acute kidney injury, acute respiratory distress syndrome, and persistent cardiogenic shock.ResultsVOT recovery slope decreased during the surgery. VOT recovery slope on postoperative day 1 was significantly lower in patients with composite complications than those without (3.1 ± 1.6 versus 4.0 ± 1.5 %/s, P = 0.001), although conventional hemodynamic values, such as cardiac output and blood pressure, did not differ between the groups. On multivariable regression and linear analyses, low VOT recovery slope on postoperative day 1 was associated with increases of composite complications (odds ratio 0.742; 95 % confidence interval (CI) 0.584 to 0.943; P = 0.015) and hospital length of stay (regression coefficient (B) −1.276; 95 % CI −2.440 to −0.112; P = 0.032).ConclusionMicrovascular reactivity largely recovered on postoperative day 1 in the patients without composite complications, but this restoration was attenuated in patients with composite complications.Trial registrationClinicalTrials.gov NCT01713192. Registered 22 October 2012.

Effects of delayed remote ischemic preconditioning on peri-operative myocardial injury in patients undergoing cardiac surgery — A randomized controlled trial

BACKGROUND Remote ischemic preconditioning (RIPC) has two time windows for organ protection: acute and delayed. Previous studies have mainly focused on the acute time window to evaluate organ protection by RIPC. We evaluated myocardial protection by delayed RIPC in adult patients undergoing cardiac surgery. METHODS A total of 160 adult patients undergoing cardiac surgery with cardiopulmonary bypass were randomized to receive either delayed RIPC (four cycles of 5min of ischemia followed by 5min of reperfusion by inflation to 200mmHg and deflation of a blood pressure cuff on the upper arm) or the control treatment 24-48h before surgery. The primary endpoint was post-operative troponin I levels serially measured for 72h. Secondary endpoints included post-operative serum creatinine levels, acute kidney injury, and composite complications. RESULTS There were no significant differences in post-operative troponin I values. The incidence of acute kidney injury, defined by the Acute Kidney Injury Network staging system, was lower in the delayed RIPC group compared to the control group (30.0% vs. 47.5%; relative risk, 0.768; 95% confidence interval, 0.599-0.985; p=0.023). Moreover, the occurrence of composite complications was lower in the delayed RIPC group compared with the control group (65.0% vs. 81.3%; relative risk, 0.536; 95% confidence interval, 0.311-0.924; p=0.020). CONCLUSIONS While RIPC did not provide cardioprotective effects in patients undergoing cardiac surgery, it appeared to reduce acute kidney injury, as well as the rate of composite complications.

Long-term clinical outcomes of Remote Ischemic Preconditioning and Postconditioning Outcome (RISPO) trial in patients undergoing cardiac surgery

BACKGROUND Remote ischemic conditioning has been shown to confer myocardial protection. However, there is still no sufficient data on its long-term clinical outcomes. We analyzed the long-term results of the Remote Ischemic Preconditioning and Postconditioning Outcome (RISPO) trial in cardiac surgery patients. METHODS In the RISPO trial, 1280 patients were randomized to receive remote ischemic preconditioning (RIPC) with postconditioning (RIPostC, upper arm ischemia by four cycles of 5-min inflation followed by 5-min deflation of a pneumatic cuff, N=644) or sham (N=636) during cardiac surgery. Patient follow-up data were collected by review of medical records, telephone interviews, and from the National Statistical Office. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE; a composite of all-cause mortality, myocardial infarction (MI), stroke, and revascularization), and the secondary endpoints were the individual components of the primary endpoint. RESULTS At completion of follow-up (mean 44months), there was no difference in MACCE between the groups (90 [14.0%] versus 101 [15.9%] in the RIPC with RIPostC versus control groups; hazard ratio [HR], 0.893; 95% confidence interval [CI], 0.672-1.187; P=0.435). However, MI was reduced to half in the RIPC with RIPostC group (10 [1.6%] versus 23 [3.6%]; HR, 0.468; 95% CI, 0.222-0.984; P=0.045). CONCLUSIONS Remote ischemic preconditioning with RIPostC did not improve long-term MACCE after cardiac surgery. However, MI was reduced in the RIPC with RIPostC group compared with the control group during the follow-up period. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov identifier, NCT00997217.

Pulmonary Protective Effects of Remote Ischaemic Preconditioning with Postconditioning in Patients Undergoing Cardiac Surgery Involving Cardiopulmonary Bypass: A Substudy of the Remote Ischaemic Preconditioning with Postconditioning Outcome trial.

BACKGROUND The RISPO (Remote Ischemic Preconditioning with Postconditioning Outcome) trial evaluated whether remote ischaemic preconditioning (RIPC) combined with remote ischaemic postconditioning (RIPostC) improves the clinical outcomes of patients undergoing cardiac surgery. This substudy of the RISPO trial aimed to evaluate the effect of RIPC with RIPostC on pulmonary function in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). METHODS Sixty-five patients were enrolled (32: control and 33: RIPC-RIPostC). In the RIPC-RIPostC group, four cycles of 5min ischaemia and 5min reperfusion were administered before and after CPB to the upper limb. Peri-operative PaO2/FIO2 ratio, intra-operative pulmonary shunt, and dynamic and static lung compliance were determined. RESULTS The mean PaO2/ FIO2 was significantly higher in the RIPC-RIPostC group at 24h after surgery [290 (96) vs. 387 (137), p=0.001]. The incidence of mechanical ventilation for longer than 48h was significantly higher in the control group (23% vs. 3%, p<0.05). However, there were no significant differences in other pulmonary profiles, post-operative mechanical ventilation time, and duration of intensive care unit stay. CONCLUSIONS In our study, RIPC-RIPostC improved the post-operative 24h PaO2/FIO2 ratio. Remote ischaemic preconditioning-Remote ischaemic postconditioning has limited and delayed pulmonary protective effects in cardiac surgery patients with CPB.

The head-down tilt position decreases vasopressor requirement during hypotension following induction of anaesthesia in patients undergoing elective coronary artery bypass graft and valvular heart surgeries.

Background and objective Previous studies have failed to demonstrate that the head-down tilt position confers benefits in hypovolaemic hypotensive patients. The aim of this study was to evaluate the haemodynamic effect and vasopressor use by this position in hypotensive patients after the induction of general anaesthesia. Methods This prospective randomised study involved 98 patients scheduled for elective cardiac surgery and 40 patients (40.1%) developed hypotension after anaesthesia induction. Upon occurrence of hypotension, patients were randomly allocated to the supine (n = 19) or head-down tilt (n = 21) groups (15° head-down tilt position). Blood pressure, heart rate, cardiac index and stroke volume index were recorded at 1-min interval for 10 min from the occurrence of hypotension. Vasopressors were administered to treat hypotension in both groups. Results No haemodynamic difference was observed between the supine and head-down tilt groups except for SBP changes from baseline at 1 min (−3.98 ± 6.31 vs. 1.84 ± 8.25%, P = 0.004) and 2 min (1.51 ± 14.34 vs. 9.37 ± 10.57%, P = 0.032). The number of vasopressor administrations and percentage of the patients requiring vasopressors in the supine group were greater than that in the head-down tilt group [median 1 (range 1–5) vs. median 0 (range 0–2), P = 0.002, 19/19 (100%) vs. 10/21 (47.6%), P < 0.001]. Conclusion The head-down tilt position in hypotensive patients following anaesthesia induction reduced vasopressor requirement by almost one third. Minimal haemodynamic effect may be caused by different vasopressor administrations. This result suggests that the head-down tilt position may enable more stable anaesthesia induction in patients undergoing elective coronary artery bypass graft or valvular heart surgeries.

Interactions of Midazolam and Propofol on α1β2γ2L and α1β2γ2S Gamma Aminobutyric Acid Type A Receptors Expressed in Human Embryonic Kidney Cells

BACKGROUND: The gamma aminobutyric acid type A (GABAA) receptor is a prime target of many anesthetics, including midazolam and propofol. Although these anesthetics have sedative and hypnotic properties by enhancing GABAA receptor activity, their interactions at the GABAA receptors have not been explored. We investigated the interaction of midazolam and propofol with &agr;1&bgr;2&ggr;2L and &agr;1&bgr;2&ggr;2S GABAA receptors. METHODS: Using the whole-cell patch clamp technique, we tested the effects of midazolam and propofol on GABA-induced currents in human embryonic kidney 293 T cells transfected with &agr;1&bgr;2&ggr;2L and &agr;1&bgr;2&ggr;2S GABAA receptors. RESULTS: Midazolam and propofol on their own enhanced the amplitude of GABAA receptor responses in a dose-dependent manner, and they had additive effects on &agr;1&bgr;2&ggr;2S GABAA receptors, but not on &agr;1&bgr;2&ggr;2L GABAA receptors. However, additive interactions of midazolam and propofol on the &agr;1&bgr;2&ggr;2L GABAA receptors were observed when protein kinase C was inhibited. CONCLUSIONS: The interaction between midazolam and propofol is affected by receptor subtype, and protein kinase phosphorylation influences their interaction on the &agr;1&bgr;2&ggr;2L receptor.