Sarah Soh

Double-blinded, randomized controlled trial of N-acetylcysteine for prevention of acute kidney injury in high risk patients undergoing off-pump coronary artery bypass

The aim of this study was to investigate the influence of perioperative N‐acetylcysteine (NAC) administration, a known antioxidant, on the incidence of acute kidney injury (AKI) after off‐pump coronary bypass surgery (OPCAB) in patients with known risk factors of AKI.

Comparison of Ramosetron and Palonosetron for Preventing Nausea and Vomiting after Spinal Surgery: Association With ABCB1 Polymorphisms.

Background: Adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) polymorphisms may influence 5-hydroxytryptamine receptor antagonist efficacy by altering their efflux transportation. We evaluated the influence of ABCB1 polymorphisms on the efficacy of ramosetron compared with palonosetron in managing postoperative nausea and vomiting (PONV) in patients who received intravenous patient-controlled analgesia after spinal surgery. Methods: Patients were randomly allocated to receive 2 boluses (20 min before the end of surgery and 24 h after surgery) of either ramosetron 0.3 mg (n=150) or palonosetron 0.075 mg (n=146). The incidence and severity of PONV, fentanyl consumption, and pain intensity were serially assessed for postoperative 48 hours. ABCB1 3435C>T and 2677G>T/A polymorphisms were assessed. Results: The incidences of nausea were similar between the 2 groups in patients with the 3435TT (50% vs. 56%, ramosetron and palonosetron group, respectively, P>0.999) or 2677TT (50% vs. 56%, ramosetron and palonosetron group, respectively, P>0.999). Mild PONV were more frequent in the ramosetron group than in the palonosetron group among patients with 3435TT (91% vs. 33%, P=0.034) and 2677TT (92% vs. 20%, P=0.002) genotypes. The intensity of nausea experienced by ramosetron-group TT genotype patients (1 [1 to 2], 3435TT; 1 [1 to 2.5], 2677TT) was lower than that experienced by ramosetron-group non-TT genotype patients (3 [1 to 6], 3435 non-TT, P=0.030; 3 [1 to 6], 2677 non-TT, P=0.038) and palonosetron-group TT genotype patients (6 [2 to 7], 3435TT, P=0.010; 6 [4 to 7], 2677TT, P=0.002). Conclusions: Compared with palonosetron, ramosetron may be superior for reducing PONV severity, especially in patients with ABCB1 3435TT or 2677TT genotype.

Postoperative Delirium in Elderly Patients Undergoing Major Spinal Surgery: Role of Cerebral Oximetry.

Background: Perioperative cerebral hypoperfusion/ischemia is a major inciting factor of postoperative delirium, which is coupled with adverse outcome in elderly patients. Cerebral oximetry enables noninvasive assessment of the regional cerebral oxygen saturation (rSO2). This study aimed to investigate whether perioperative rSO2 variations were linked to delirium in elderly patients after spinal surgery. Materials and Methods: Postoperative delirium was assessed for 48 hours postsurgery in 109 patients aged over 60 years without a prior history of cerebrovascular or psychiatric diseases by the Confusion Assessment Method for the intensive care unit and the intensive care delirium screening checklist. The rSO2 values immediately before and throughout surgery were acquired. The preoperative cognitive functions, patient characteristics, and perioperative data were recorded. Results: During the 48-h postoperative period, 9 patients (8%) exhibited delirium. The patients with delirium showed similar perioperative rSO2 values as those without, in terms of the median lowest rSO2 values (55% vs. 56%; P=0.876) and incidence (22%, both) and duration of decline of rSO2<80% of the baseline values. The serially assessed hemodynamic variables, hematocrit levels, and blood gas analysis variables were also similar between the groups, except for the number of hypotensive events per patient, which was higher in the patients with delirium than in those without (4, interquartile range [IQR] 3 to 6 vs. 2, IQR: 1to 3; P=0.014). Conclusions: The degree and duration of decrease of the perioperative rSO2 measurements were not associated with delirium in elderly patients after spinal surgery.

Sodium bicarbonate does not prevent postoperative acute kidney injury after off-pump coronary revascularization: a double-blinded randomized controlled trial

BACKGROUND Acute kidney injury (AKI) is a common morbidity after off-pump coronary revascularization. We investigated whether perioperative administration of sodium bicarbonate, which might reduce renal injury by alleviating oxidative stress in renal tubules, prevents postoperative AKI in off-pump coronary revascularization patients having renal risk factors. METHODS Patients (n=162) having at least one of the following AKI risk factors were enrolled: (i) age >70 yr; (ii) diabetes mellitus; (iii) chronic renal disease; (iv) congestive heart failure or left ventricular ejection fraction <35%; and (v) reoperation or emergency. Patients were evenly randomized to receive either sodium bicarbonate (0.5 mmol kg-1 for 1 h upon induction of anaesthesia followed by 0.15 mmol kg-1 h-1 for 23 h) or 0.9% saline. Acute kidney injury within 48 h after surgery was assessed using the Acute Kidney Injury Network criteria. RESULTS The incidences of AKI were 21 and 26% in the bicarbonate and control groups, respectively (P=0.458). Serially measured serum creatinine concentrations and perioperative fluid balance were also comparable between the groups. The length of postoperative hospitalization and incidence of morbidity end points were similar between the groups, whereas significantly more patients in the bicarbonate group required prolonged mechanical ventilation (>24 h) relative to the control group (20 vs 6, P=0.003). CONCLUSIONS Perioperative sodium bicarbonate administration did not decrease the incidence of AKI after off-pump coronary revascularization in high-risk patients and might even be associated with a need for prolonged ventilatory care. CLINICAL TRIAL REGISTRATION NCT01840241.

Dual antiplatelet therapy and non-cardiac surgery: evolving issues and anesthetic implications

Dual antiplatelet therapy (DAPT) consisting of aspirin plus a P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) is imperative for the treatment of acute coronary syndrome, particularly during the re-endothelialization period after percutaneous coronary intervention (PCI). When patients undergo surgery during this period, the consequences of stent thrombosis are far more serious than those of bleeding complications, except in cases of intracranial surgery. The recommendations for perioperative DAPT have changed with emerging evidence regarding the improved efficacy of non-first-generation drug (everolimus, zotarolimus)-eluting stents (DES). The mandatory interval of 1 year for elective surgery after DES implantation was shortened to 6 months (3 months if surgery cannot be further delayed). After this period, it is generally recommended that the P2Y12 inhibitor be stopped for the amount of time necessary for platelet function recovery (clopidogrel 5–7 days, prasugrel 7–10 days, ticagrelor 3–5 days), and that aspirin be continued during the perioperative period. In emergent or urgent surgeries that cannot be delayed beyond the recommended period after PCI, proceeding to surgery with continued DAPT should be considered. For intracranial procedures or other selected surgeries in which increased bleeding risk may also be fatal, cessation of DAPT (possibly with continuation or minimized interruption [3–4 days] of aspirin) with bridge therapy using short-acting, reversible intravenous antiplatelet agents such as cangrelor (P2Y12 inhibitor) or glycoprotein IIb/IIIa inhibitors (tirofiban, eptifibatide) may be contemplated. Such a critical decision should be individually tailored based on consensus among the anesthesiologist, cardiologist, surgeon, and patient to minimize both ischemic and bleeding risks.

Patient-controlled Analgesia With Propacetamol-Fentanyl Mixture for Prevention of Postoperative Nausea and Vomiting in High-risk Patients Undergoing Spine Surgery: A Randomized Controlled Trial.

Background: This randomized trial evaluated the effect of intravenous patient-controlled analgesia (IV-PCA) based on fentanyl mixed with either propacetamol or an equivalent volume of normal saline on postoperative nausea and vomiting (PONV) in highly susceptible patients undergoing spinal surgery. Materials and Methods: One hundred eight nonsmoking female patients were randomly and evenly allocated to receive IV-PCA with either propacetamol (4 g) or normal saline mixed to fentanyl (20 &mgr;g/kg). Primary study outcome was PONV incidence at 24 hours postsurgery. Secondary outcomes were nausea severity, pain intensity (100-mm visual analog scale), use of rescue antiemetics and analgesics, patient satisfaction, and adverse events at 6, 12, and 24 hours postsurgery. Results: Postsurgery, the propacetamol versus normal saline group had lower PONV incidence at 24 hours (41% vs. 66%, P=0.011); pain intensity at rest and rescue analgesic requirements at 6 to 12 hours (30±15 vs. 41±19, P=0.008; and 25% vs. 49%, P=0.036, respectively) and at 12 to 24 hours (25±15 vs. 35±17, P=0.008; and 19% vs. 42%, P=0.044, respectively); and higher patient satisfaction score (6.4±1.4 vs. 5.7±1.8, P=0.028). Conclusions: In patients undergoing spinal surgery and at risk of developing PONV, continuous IV-PCA based on propacetamol mixed to fentanyl, relative to fentanyl alone, effectively reduced the incidence of PONV, pain intensity at rest, and additional use of rescue analgesics with higher patient satisfaction.

Prognostic role of carotid intima-media thickness in off-pump coronary artery bypass surgery

Carotid intima-media thickness (IMT) is a well-known predictor of adverse outcomes in the ischemic heart disease patients; however, evidence is lacking in patients undergoing off-pump coronary artery bypass surgery (OPCAB). Data from 407 patients who underwent OPCAB between April 2013 and August 2016 were retrospectively reviewed. A composite of cardiovascular morbidity endpoints was defined as the presence of stroke, acute myocardial infarction, new cardiac arrhythmia (newly developed atrial fibrillation, atrial flutter, or atrioventricular block), cardiovascular death, or cerebrovascular death within 30 days after surgery. Increased carotid IMT was defined as ≥0.9 mm on one or both sides. The incidence of a composite of cardiovascular morbidity endpoints was 24.0% in the normal IMT group (n = 221) and 34.4% in the increased IMT group (n = 186) (p = 0.021). Multivariable analysis revealed increased IMT (odds ratio 1.719, 95% confidence interval 1.108 to 2.666, p = 0.016) and preoperative renal replacement therapy (odds ratio 4.264, 95% confidence interval 1.679 to 10.829, p = 0.002) as independent predictors of a composite of cardiovascular morbidity endpoints. In patients undergoing OPCAB, preoperative assessment of carotid IMT may help predicting the development of a postoperative composite of cardiovascular morbidity endpoints.

Ethyl pyruvate attenuates myocardial ischemia-reperfusion injury exacerbated by hyperglycemia via retained inhibitory effect on HMGB1

BACKGROUND Hyperglycemia (HG) exacerbates myocardial ischemia/reperfusion (I/R) injury and renders protective strategies ineffective by amplified inflammatory response via enhanced high-mobility group box-1 (HMGB1) release. This study investigated the role of ethyl pyruvate (EP) against myocardial I/R injury under a clinically relevant HG condition. METHODS Sprague-Dawley rats (n=76) were randomly assigned to 6 groups: normoglycemia (NG)-Sham, NG-I/R-control (C, saline), NG-I/R-EP treatment (50mg/kg) upon reperfusion, HG-Sham, HG-I/R-C, and HG-I/R-EP treatment upon reperfusion. HG was induced by 1.2g/kg dextrose. I/R was induced by ligation of the left anterior descending artery for 30min followed by 4h of reperfusion. RESULTS HG resulted in exacerbation of myocardial infarct size by 19% with amplified activation of HMGB1-receptors of advanced glycation end products/toll like receptors-NF-κB pathway compared to NG following I/R, which all could be attenuated by EP. EP treatment was associated with diminished tumor necrosis factor-α, interleukin-1β, and interleukin-6 expressions. It also served to normalize the increase in pro-apoptotic Bax and the decrease in anti-apoptotic Bcl-2 protein levels. These effects were associated with decreased myocardial apoptosis and infarct size (by 30% and 36% in the NG and HG groups, respectively) regardless of the glycemic condition. CONCLUSION HG exacerbated myocardial I/R injury through amplified inflammatory response via increased HMGB1 level. EP treatment upon reperfusion conveyed significant myocardial protection against the I/R injury under both NG and HG conditions. Common to both glycemic conditions, associated mechanisms involved attenuated increase in HMGB1 level and suppression of its down-stream pathways.

Skin perfusion pressure as an indicator of tissue perfusion in valvular heart surgery: Preliminary results from a prospective, observational study

Hemodynamic management aims to provide adequate tissue perfusion, which is often altered during cardiac surgery with cardiopulmonary bypass (CPB). We evaluated whether skin perfusion pressure (SPP) can be used for monitoring of adequacy of tissue perfusion in patients undergoing valvular heart surgery. Seventy-two patients undergoing valve replacement were enrolled. SPP and serum lactate level were assessed after anaesthesia induction (baseline), during CPB, after CPB-off, end of surgery, arrival at intensive care unit, and postoperative 6 h. Lactate was further measured until postoperative 48 h. Association of SPP with lactate and 30-day morbidity comprising myocardial infarction, acute kidney injury, stroke, prolonged intubation, sternal infection, reoperation, and mortality was assessed. Among the lactate levels, postoperative 6 h peak value was most closely linked to composite of 30-day morbidity. The SPP value during CPB and its % change from the baseline value were significantly associated with the postoperative 6 h peak lactate (r = -0.26, P = 0.030 and r = 0.47, P = 0.001, respectively). Optimal cut-off of % decrease in SPP during CPB from baseline value for the postoperative 6 h hyperlactatemia was 48% (area under curve, 0.808; 95% confidence interval (CI), 0.652–0.963; P = 0.001). Decrease in SPP >48% during CPB from baseline value was associated with a 12.8-fold increased risk of composite endpoint of 30-day morbidity (95% CI, 1.48–111.42; P = 0.021) on multivariate logistic regression. Large decrease in SPP during CPB predicts postoperative 6 h hyperlactatemia and 30-day morbidity, which implicates a promising role of SPP monitoring in the achievement of optimal perfusion during CPB.

Ventilation With High or Low Tidal Volume With PEEP Does Not Influence Lung Function After Spinal Surgery in Prone Position: A Randomized Controlled Trial

Background: Spinal surgery in the prone position is accompanied by increased intrathoracic pressure and decreased respiratory compliance. This study investigated whether intraoperative lung protective mechanical ventilation improved lung function evaluated with pulmonary function tests in patients at risk of postoperative pulmonary complications (PPCs) after major spinal surgery in the prone position. Methods: Seventy-eight patients at potential risk of PPCs were randomly assigned to the protective group (tidal volume; 6 mL/kg predicted body weight, 6 cm H2O positive end-expiratory pressure with recruitment maneuvers) or the conventional group (10 mL/kg predicted body weight, no positive end-expiratory pressure). The primary efficacy variables were assessed by pulmonary function tests, performed before surgery, and 3 and 5 days afterward. Results: Postoperative forced vital capacity (2.17±0.1 L vs. 1.91±0.1 L, P=0.213) and forced expiratory volume in 1 second (1.73±0.08 L vs. 1.59±0.08 L, P=0.603) at postoperative day (POD) 3 in the protective and conventional groups, respectively, were similar. Trends of a postoperative decrease in forced vital capacity (P=0.586) and forced expiratory volume in 1 second (P=0.855) were similar between the groups. Perioperative blood-gas analysis variables were comparable between the groups. Patients in the protective and conventional groups showed similar rates of clinically significant PPCs (8% vs. 10%, P>0.999). Conclusions: In patients at potential risk of developing PPCs undergoing major spinal surgery, we did not find evidence indicating any difference between the lung protective and conventional ventilation in postoperative pulmonary function and oxygenation.