Sun-Kyung Park

Sevoflurane post-conditioning increases nuclear factor erythroid 2-related factor and haemoxygenase-1 expression via protein kinase C pathway in a rat model of transient global cerebral ischaemia

BACKGROUND The antioxidant mechanism of sevoflurane post-conditioning-induced neuroprotection remains unclear. We determined whether sevoflurane post-conditioning induces nuclear factor erythroid 2-related factor (Nrf2, a master transcription factor regulating antioxidant defence genes) and haemoxygenase-1 (HO-1, an antioxidant enzyme) expression, and whether protein kinase C (PKC) is involved in Nrf2 activation, in a rat model of transient global cerebral ischaemia/reperfusion (I/R) injury. METHODS Eighty-six rats were assigned to five groups: sham (n=6), control (n=20), sevoflurane post-conditioning (two cycles with 2 vol% sevoflurane inhalation for 10 min, n=20), chelerythrine (a PKC inhibitor; 5 mg kg(-1) i.v. administration, n=20), and sevoflurane post-conditioning plus chelerythrine (n=20). The levels of nuclear Nrf2 and cytoplasmic HO-1 were assessed 1 or 7 days after ischaemia (n=10 each, apart from the sham group, n=3). RESULTS On day 1 but not day 7 post-ischaemia, Nrf2 and HO-1 expression were significantly higher in the sevoflurane post-conditioning group than in the control group. Chelerythrine administration reduced the elevated Nrf2 and HO-1 expression induced by sevoflurane post-conditioning. CONCLUSIONS Sevoflurane post-conditioning increased Nrf2/HO-1 expression via PKC signalling in the early phase after transient global cerebral I/R injury, suggesting that activation of antioxidant enzymes may be responsible for sevoflurane post-conditioning-induced neuroprotection in the early phase after cerebral I/R injury.

Analysis of patterns of three-phase bone scintigraphy for patients with complex regional pain syndrome diagnosed using the proposed research criteria (the ‘Budapest Criteria’)

BACKGROUND Three-phase bone scintigraphy (TPBS) is an established objective diagnostic method for complex regional pain syndrome (CRPS), but its validity remains controversial. The aims of this study were: (i) to re-evaluate the diagnostic performance of TPBS, and (ii) to suggest new TPBS criteria based on the proposed research criteria for CPRS in Budapest (the 2003 Budapest research criteria). METHODS The medical records of 228 consecutive patients, evaluated using the Budapest research criteria, were retrospectively analysed. Of these, 116 patients were included in the present study, and 69 of 116 were diagnosed to have CRPS based on these criteria. The diagnostic performance of TPBS was assessed by determining its sensitivity, specificity, and positive and negative likelihood ratios, and new criteria for TPBS were identified by pattern analysis using the Budapest research criteria. RESULTS The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of TPBS for the diagnosis of CRPS according to the Budapest research criteria were 40.0, 76.5, 1.73, and 0.78, respectively. Furthermore, D-D-D, D-D-S, and D-D-I patterns [i.e. according to decreased (D), symmetrical (S), or increased (I) tracer uptake during Phases I, II, and III] of TPBS were found to be positively predictive for CRPS. CONCLUSIONS The diagnostic value of a positive TPBS for CRPS is low from the view point of the Budapest research criteria. Our findings suggest that a diagnosis of CRPS using the Budapest research criteria should be considered when decreased patterns of TPBS are observed during Phases I and II.

Risk Factors for Acute Kidney Injury after Congenital Cardiac Surgery in Infants and Children: A Retrospective Observational Study

Acute kidney injury (AKI) after pediatric cardiac surgery is associated with high morbidity and mortality. Modifiable risk factors for postoperative AKI including perioperative anesthesia-related parameters were assessed. The authors conducted a single-center, retrospective cohort study of 220 patients (aged 10 days to 19 years) who underwent congenital cardiac surgery between January and December 2012. The incidence of AKI within 7 days postoperatively was determined using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Ninety-two patients (41.8%) developed AKI and 18 (8.2%) required renal replacement therapy within the first postoperative week. Among patients who developed AKI, 57 patients (25.9%) were KDIGO stage 1, 27 patients (12.3%) were KDIGO stage 2, and eight patients (3.6%) were KDIGO stage 3. RACHS-1 (Risk-Adjusted classification for Congenital Heart Surgery) category, perioperative transfusion and fluid administration as well as fluid overload were compared between patients with and without AKI. Multivariable logistic regression analyses determined the risk factors for AKI. AKI was associated with longer hospital stay or ICU stay, and frequent sternal wound infections. Younger age (<12 months) [odds ratio (OR), 4.01; 95% confidence interval (CI), 1.77–9.06], longer cardiopulmonary bypass (CPB) time (OR, 2.45; 95% CI, 1.24–4.84), and low preoperative hemoglobin (OR, 2.40; 95% CI, 1.07–5.40) were independent risk factors for AKI. Fluid overload was not a significant predictor for AKI. When a variable of hemoglobin concentration increase (>3 g/dl) from preoperative level on POD1 was entered into the multivariable analysis, it was independently associated with postoperative AKI (OR, 6.51; 95% CI, 2.23–19.03 compared with no increase). This association was significant after adjustment with patient demographics, medication history and RACHS-1 category (hemoglobin increase >3g/dl vs. no increase: adjusted OR, 6.94; 95% CI, 2.33–20.69), regardless of different age groups and cyanotic or non-cyanotic heart disease. Prospective trials are required to evaluate whether correction of preoperative anemia and prevention of hemoconcentration may ameliorate postoperative AKI in patients who underwent congenital cardiac surgery.

The effect of early goal-directed therapy for treatment of severe sepsis or septic shock: A systemic review and meta-analysis

Purpose: To assess the effects of early goal‐directed therapy (EGDT) on reducing mortality compared with conventional management of severe sepsis or septic shock. Materials and methods: We included a systemic review, using the Medline and EMBASE. Seventeen randomized trials with 5765 patients comparing EGDT with usual care were included. Results: There were no significant differences in mortality between EGDT and control groups (relative risk [RR], 0.89; 95% confidence interval [CI], 0.79‐1.00), with moderate heterogeneity (I2 = 56%). The EGDT was associated with lower mortality rates when the mortality rate of the usual care group was greater than 30% (12 trials; RR, 0.83; 95% CI, 0.72‐0.96), but not when the mortality rate in the usual care group was less than 30% (5 trials; RR, 1.03; 95% CI, 0.92‐1.16). The mortality benefit was seen only in subgroup of population analyzed between publication of the 2004 and 2012 Surviving Sepsis Campaign guidelines, but not before and after these publications. Conclusion: This meta‐analysis was heavily influenced by the recent addition of the trio of trials published after 2014. The results of the recent trio of trials may be biased due to methodological issues. This includes lack of blinding by incorporating similar diagnostic and therapeutic interventions as the original EGDT trial.

Comparison of Supraclavicular and Infraclavicular Brachial Plexus Block: A Systemic Review of Randomized Controlled Trials

BACKGROUND: Supraclavicular (SC) and infraclavicular (IC) brachial plexus block (BPB) are commonly used for upper extremity surgery. Recent clinical studies have compared the effect of SC- and IC-BPB, but there have been controversies over spread of sensory blockade in each of the 4 peripheral nerve branches of brachial plexus. METHODS: This study included a systemic review, using the Medline and EMBASE database from their inceptions through March 2016. Randomized controlled trials (RCTs) comparing SC- and IC-BPB were included. The prespecified primary outcome was the incidences of incomplete sensory blockade in each of the 4 terminal nerve branches of brachial plexus. Secondary outcome included the incidence of successful blockade, performance time, onset of sensory block, duration of analgesia, and complication rates. RESULTS: Ten RCTs involving 676 patients were included. Pooled analyses showed the incidence of incomplete block at 30 minutes in radial nerve territory was significantly higher in IC-BPB, favoring SC-BPB (risk ratio 0.39; 95% confidence interval [0.17–0.88], P = .02, I2 = 0%). However, subgroup analysis according to the number of injections of IC-BPB showed that double or triple injections IC-BPB yielded no difference in the incomplete radial block. Furthermore, the incidence of incomplete ulnar block at 30 minutes was significantly lower in IC-BPB when using double or triple injection IC-BPB. There was no difference in the secondary outcomes between SC- and IC-BPB groups, with the exception of complication rates. The incidence of paresthesia/pain on local anesthetic injection, phrenic nerve palsy, and Horner syndrome was significantly higher in the SC group, favoring IC-BPB. CONCLUSIONS: This meta-analysis demonstrated that IC-BPB showed a significantly high incidence of incomplete radial nerve sensory block at 30 minutes, which may be avoided by double or triple injection. Furthermore, IC-BPB with multiple injection technique showed significantly lower incidence of incomplete ulnar block than SC-BPB. There were no differences in the incidence of successful blockade, block onset, and duration of analgesia between SC- and IC-BPB. Procedure-related paresthesia/pain and adjacent nerve-related complications were more frequent in SC-BPB. However, because of the small sample size, publication bias remains a concern when interpreting our results. Further studies with sufficient sample size and reporting large number of outcomes are required.

Preoperative aspirin use and acute kidney injury after cardiac surgery: A propensity-score matched observational study

Background The association between preoperative aspirin use and postoperative acute kidney injury (AKI) in cardiovascular surgery is unclear. We sought to evaluate the effect of preoperative aspirin use on postoperative AKI in cardiac surgery. Methods A total of 770 patients who underwent cardiovascular surgery under cardiopulmonary bypass were reviewed. Perioperative clinical parameters including preoperative aspirin administration were retrieved. We matched 108 patients who took preoperative aspirin continuously with patients who stopped aspirin more than 7 days or did not take aspirin for the month before surgery. The parameters used in the matching included variables related to surgery type, patient’s demographics, underlying medical conditions and preoperative medications. Results In the first seven postoperative days, 399 patients (51.8%) developed AKI, as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria and 128 patients (16.6%) required hemodialysis. Most patients took aspirin 100 mg once daily (n = 195, 96.5%) and the remaining 75 mg once daily. Multivariable analysis showed that preoperative maintenance of aspirin was independently associated with decreased incidence of postoperative AKI (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.21–0.98, P = 0.048; after propensity score matching: OR 0.39, 95% CI 0.22–0.67, P = 0.001). Preoperative maintenance of aspirin was associated with less incidence of AKI defined by KDIGO both in the entire and matched cohort (n = 44 [40.7%] vs. 69 [63.9%] in aspirin and non-aspirin group, respectively in matched sample, relative risk [RR] 0.64, 95% CI 0.49, 0.83, P = 0.001). Preoperative aspirin was associated with decreased postoperative hospital stay after matching (12 [9–18] days vs. 16 [10–25] in aspirin and non-aspirin group, respectively, P = 0.038). Intraoperative estimated or calculated blood loss using hematocrit difference and estimated total blood volume showed no difference according to aspirin administration in both entire and matched cohort. Conclusions Preoperative low dose aspirin administration without discontinuation was protective against postoperative AKI defined by KDIGO criteria independently in both entire and matched cohort. Preoperative aspirin was also associated with decreased hemodialysis requirements and decreased postoperative hospital stay without increasing bleeding. However, differences in AKI and hospital stay were not associated with in-hospital mortality.

Risk of non-cardiac surgery after percutaneous coronary intervention with drug-eluting stents

Elective non-cardiac surgery (NCS) should optimally be delayed one year after implantation of a drug-eluting stent (DES). Dual antiplatelet therapy or at least aspirin is recommended to be continued considering the relative risk of stent thrombosis especially during the 4 weeks after DES implantation. However, these recommendations were supported by insufficient evidence. We investigated predictors for postoperative major adverse cardiovascular and cerebral event (MACCE) in 1582 patients undergoing non-cardiac surgery after DES implantation. 96 patients (6.1%) developed postoperative MACCE. In the propensity score-matched analysis, aspirin maintenance was not associated with MACCE (odds ratio [OR] 0.78, 95% confidence interval [CI] 0.48–1.27, P = 0.320) and was associated with increased risk of major bleeding (OR 1.84, 95% CI 1.02–3.32, P = 0.044). When patients who underwent NCS within one month after DES implantation were matched with those who underwent NCS thereafter, the risk of MACCE was higher when surgery was done within 30 days after PCI (OR 2.21, 95% CI 1.05–4.66, P = 0.036). Maintenance of aspirin did not decrease MACCE after NCS in patients with DES and only increased the risk of major bleeding. NCS within one month after DES implantation was associated with higher incidence of MACCE. However, prospective trials are required to validate our results.

Predictive Value of Intraoperative Thromboelastometry for the Risk of Perioperative Excessive Blood Loss in Infants and Children Undergoing Congenital Cardiac Surgery: A Retrospective Analysis

OBJECTIVE Laboratory hemostatic variables and parameters of rotational thromboelastometry (ROTEM) were evaluated for their ability to predict perioperative excessive blood loss (PEBL) after congenital cardiac surgery. DESIGN Retrospective and observational. SETTING Single, large university hospital. PARTICIPANTS The study comprised 119 children younger than 10 years old undergoing congenital cardiac surgery with cardiopulmonary bypass (CPB). MEASUREMENTS AND MAIN RESULTS Intraoperative excessive blood loss was defined as estimated blood loss≥50% of estimated blood volume (EBV). Postoperative excessive blood loss was defined as measured postoperative chest tube and Jackson-Pratt drainage≥30% of EBV over 12 hours or≥50% of EBV over 24 hours in the intensive care unit. PEBL was defined as either intraoperative or postoperative excessive blood loss. External temogram (EXTEM) and fibrinogen temogram (FIBTEM) were analyzed before and after CPB with ROTEM and laboratory hemostatic variables. Multivariate logistic regression was performed. Incidence of PEBL was 19.3% (n = 23). Independent risk factors for PEBL were CPB time>120 minutes, post-CPB FIBTEM alpha-angle, clot firmness after 10 minutes<5 mm, post-CPB EXTEM alpha-angle, clot firmness after 10 minutes<30 mm, and post-CPB EXTEM maximal lysis>20%. Laboratory hemostatic variables were not significant in multivariate analysis. The risk prediction model was developed from the results of multivariate analysis. The area under the receiver operating characteristic curve was 0.94 (95% confidence interval: 0.90-0.99). CONCLUSIONS Post-CPB ROTEM may be useful for predicting both intraoperative and postoperative excessive blood loss in congenital cardiac surgery. This study provided an accurate prediction model for PEBL and supported intraoperative transfusion guidance using post-CPB FIBTEM-A10 and EXTEM-A10.

Association of nefopam use with postoperative nausea and vomiting in gynecological patients receiving prophylactic ramosetron: A retrospective study

Background Postoperative nausea and vomiting (PONV) is a common adverse effect of opioid-based intravenous patient-controlled analgesia (IV PCA). Nefopam has been considered as a good candidate for inclusion in multimodal analgesia because of its opioid sparing effect, but it can be emetic. This study aims to examine whether the use of nefopam combined with fentanyl in IV PCA was associated with the higher incidence of PONV in patients receiving prophylactic ramosetron after gynecological surgery. Methods Data from 296 patients who underwent gynecological surgery were retrospectively reviewed. The patients received IV PCA containing either fentanyl 1500 μg and ketorolac 90 mg (Group K) or fentanyl 1500 μg and nefopam 80 mg (Group N). All patients in both groups received 0.3 mg of ramosetron at the end of surgery. The primary outcome measure was the incidence of PONV during the 3-day postoperative period. Results No difference was observed in the incidence of PONV during the 3-day postoperative period between the two groups. However, the incidence of nausea on postoperative day 2 was significantly higher in Group N (10.3%) than in Group K (2.8%) (P = 0.016). Multivariable logistic regression analysis showed that the use of nefopam was not associated with a higher incidence of PONV (adjusted odds ratio, 1.616; 95% confidence interval, 0.952–2.743, P = 0.076). There were no differences in postoperative pain scores between the two groups. Conclusion The combined use of nefopam with fentanyl in IV PCA was not associated with the higher incidence of PONV compared with the use of ketorolac and fentanyl combination in patients who received ramosetron as PONV prophylactic agent. However, prospective trials are required for a confirmative conclusion.

Acute kidney injury in parturients with severe preeclampsia

We read with interest the study by Mazda et al. [1] regarding postoperative acute kidney injury (AKI) in parturients with severe preeclamsia. We would like to discuss the clinical implication of the study. First, the effect of hydroxyl ethyl starch (HES) administration was not evaluated fully. Clinical outcomes other than AKI were not compared with a control group. Although not clearly shown, the number of patients with proteinuria or elevated serum creatinine seems to be very small. The incidence of AKI and the impact of HES on AKI may be different in the more selected patients with severe preeclampsia with renal dysfunction [2]. Second, the serum creatinine measurement may not be a reliable estimation of glomerular filtration rate (GFR) in these parturients [3]. Delivery itself and different oral intakes after surgery may influence serum creatinine and following creatinine after delivery may not be accurate. GFR increases up to 50% during pregnancy and continue at levels 20% above normal at postpartum week [4]. Diagnosis of AKI in these patients using other measurement of GFR or more sensitive biomarkers may be required.