Benefits and Harms of Procalcitonin- or C-Reactive Protein-Guided Antimicrobial Discontinuation in Critically Ill Adults With Sepsis: A Systematic Review and Network Meta-Analysis.

OBJECTIVES: In sepsis treatment, antibiotics are crucial, but overuse risks development of antibiotic resistance. Recent guidelines recommended the use of procalcitonin to guide antibiotic cessation, but solid evidence is insufficient. Recently, concerns were raised that this strategy would increase recurrence. Additionally, optimal protocol or difference from the commonly used C-reactive protein (CRP) are uncertain. We aimed to compare the effectiveness and safety of procalcitonin- or CRP-guided antibiotic cessation strategies with standard of care in sepsis. DATA SOURCES: A systematic search of PubMed, Embase, CENTRAL, Igaku Chuo Zasshi, ClinicalTrials.gov, and World Health Organization International Clinical Trials Platform. STUDY SELECTION: Randomized controlled trials involving adults with sepsis in intensive care. DATA EXTRACTION: A systematic review with network meta-analyses was performed. The Grading of Recommendations, Assessments, Developments, and Evaluation method was used to assess certainty. DATA SYNTHESIS: Eighteen studies involving 5023 participants were included. Procalcitonin-guided and CRP-guided strategies shortened antibiotic treatment (-1.89 days [95% CI, -2.30 to -1.47], -2.56 days [95% CI, -4.21 to -0.91]) with low- to moderate-certainty evidence. In procalcitonin-guided strategies, this benefit was consistent even in subsets with shorter baseline antimicrobial duration (7-10 d) or in Sepsis-3, and more pronounced in procalcitonin cutoff of "0.5 µg/L and 80% reduction." No benefit was observed when monitoring frequency was less than half of the initial 10 days. Procalcitonin-guided strategies lowered mortality (-27 per 1000 participants [95% CI, -45 to -7]) and this was pronounced in Sepsis-3, but CRP-guided strategies led to no difference in mortality. Recurrence did not increase significantly with either strategy (very low to low certainty). CONCLUSIONS: In sepsis, procalcitonin- or CRP-guided antibiotic discontinuation strategies may be beneficial and safe. In particular, the usefulness of procalcitonin guidance for current Sepsis-3, where antimicrobials are used for more than 7 days, was supported. Well-designed studies are needed focusing on monitoring protocol and recurrence.

Prognostic evaluation of quick sequential organ failure assessment score in ICU patients with sepsis across different income settings.

BACKGROUND: There is conflicting evidence on association between quick sequential organ failure assessment (qSOFA) and sepsis mortality in ICU patients. The primary aim of this study was to determine the association between qSOFA and 28-day mortality in ICU patients admitted for sepsis. Association of qSOFA with early (3-day), medium (28-day), late (90-day) mortality was assessed in low and lower middle income (LLMIC), upper middle income (UMIC) and high income (HIC) countries/regions. METHODS: This was a secondary analysis of the MOSAICS II study, an international prospective observational study on sepsis epidemiology in Asian ICUs. Associations between qSOFA at ICU admission and mortality were separately assessed in LLMIC, UMIC and HIC countries/regions. Modified Poisson regression was used to determine the adjusted relative risk (RR) of qSOFA score on mortality at 28 days with adjustments for confounders identified in the MOSAICS II study. RESULTS: Among the MOSAICS II study cohort of 4980 patients, 4826 patients from 343 ICUs and 22 countries were included in this secondary analysis. Higher qSOFA was associated with increasing 28-day mortality, but this was only observed in LLMIC (p < 0.001) and UMIC (p < 0.001) and not HIC (p = 0.220) countries/regions. Similarly, higher 90-day mortality was associated with increased qSOFA in LLMIC (p < 0.001) and UMIC (p < 0.001) only. In contrast, higher 3-day mortality with increasing qSOFA score was observed across all income countries/regions (p < 0.001). Multivariate analysis showed that qSOFA remained associated with 28-day mortality (adjusted RR 1.09 (1.00-1.18), p = 0.038) even after adjustments for covariates including APACHE II, SOFA, income country/region and administration of antibiotics within 3 h. CONCLUSIONS: qSOFA was independently associated with 28-day mortality in ICU patients admitted for sepsis. In LLMIC and UMIC countries/regions, qSOFA was associated with early to late mortality but only early mortality in HIC countries/regions.

Ubiquitination of the µ-opioid receptor regulates receptor internalization without affecting Gi/o-mediated intracellular signaling or receptor phosphorylation.

Opioids are highly potent analgesics but develop tolerance. Previous studies have focused on phosphorylation of the µ-opioid receptor as it is involved in maintaining cellular sensitivity via desensitization, recycling, and degradation of the activated receptor. Recently, ubiquitination, another form of posttranslational modification has attracted attention in terms of triggering intracellular signaling and regulation of the activated receptor. Here, we generated a ubiquitination-deficient mutant of the µ-opioid receptor to investigate whether ubiquitination is involved in driving Gi/o-mediated analgesic signaling, receptor desensitization or subsequent receptor internalization. Our study shows that the Gi/o pathway and receptor phosphorylation do not require ubiquitination. Instead, ubiquitination regulates the internalization efficiency and might help in promoting internalization of the desensitized MOP.

Platelet function of whole blood after short-term cold storage: A prospective in vitro observational study.

BACKGROUND: There is no standardized storage temperature of whole blood for acute normovolemic hemodilution (ANH). STUDY DESIGN AND METHODS: We conducted a prospective observational study to examine the difference in platelet function between short-term whole blood storage at 4 and 22°C. Venous blood (40 ml) was collected from seven healthy subjects who gave prior written consent. The samples were divided into three groups: before storage (group Pre), cold (4°C) storage (group C), and room temperature (22°C) storage (group R). Groups C and R were tested after 6 h of blood storage. Platelet aggregability, platelet factor 4 (PF4), ß-thromboglobulin (ß-TG), P-selectin expression, pH, PO2 , PCO2 , glucose, lactate, blood count, and thromboelastography (TEG) parameters were measured. The percentage change in each parameter in groups C and R was calculated using the value in group Pre as a reference. These data were then compared between groups C and R using a Wilcoxon matched pairs test. p < 0.05 was considered to be statistically significant. RESULTS: Compared with group R, group C showed significantly higher platelet aggregability with adenosine diphosphate (ADP) 2, 4, and 6 µM (all p = 0.016) and collagen 1 µg/ml (p = 0.047) stimulation, and significantly lower PF4 and ß-TG elevation (both p = 0.031), glucose consumption (p = 0.031), and lactate production (p = 0.016). The ADP channel in TEG showed a significant increase in platelet aggregation rate in group C compared to group R. DISCUSSION: Cold storage of whole blood in ANH may provide improved storage conditions for platelets and contribute to improved hemostasis compared to room temperature storage.

Epidemiology, Management, and Outcomes of Sepsis in ICUs among Countries of Differing National Wealth across Asia.

Rationale: Directly comparative data on sepsis epidemiology and sepsis bundle implementation in countries of differing national wealth remain sparse. Objectives: To evaluate across countries/regions of differing income status in Asia 1) the prevalence, causes, and outcomes of sepsis as a reason for ICU admission and 2) sepsis bundle (antibiotic administration, blood culture, and lactate measurement) compliance and its association with hospital mortality. Methods: A prospective point prevalence study was conducted among 386 adult ICUs from 22 Asian countries/regions. Adult ICU participants admitted for sepsis on four separate days (representing the seasons of 2019) were recruited. Measurements and Main Results: The overall prevalence of sepsis in ICUs was 22.4% (20.9%, 24.5%, and 21.3% in low-income countries/regions [LICs]/lower middle-income countries/regions [LMICs], upper middle-income countries/regions, and high-income countries/regions [HICs], respectively; P < 0.001). Patients were younger and had lower severity of illness in LICs/LMICs. Hospital mortality was 32.6% and marginally significantly higher in LICs/LMICs than HICs on multivariable generalized mixed model analysis (adjusted odds ratio, 1.84; 95% confidence interval, 1.00-3.37; P = 0.049). Sepsis bundle compliance was 21.5% at 1 hour (26.0%, 22.1%, and 16.2% in LICs/LMICs, upper middle-income countries/regions, and HICs, respectively; P < 0.001) and 36.6% at 3 hours (39.3%, 32.8%, and 38.5%, respectively; P = 0.001). Delaying antibiotic administration beyond 3 hours was the only element independently associated with increased mortality (adjusted odds ratio, 2.53; 95% confidence interval, 2.07-3.08; P < 0.001). Conclusions: Sepsis is a common cause of admission to Asian ICUs. Mortality remains high and is higher in LICs/LMICs after controlling for confounders. Sepsis bundle compliance remains low. Delaying antibiotic administration beyond 3 hours from diagnosis is associated with increased mortality. Clinical trial registered with www.ctri.nic.in (CTRI/2019/01/016898).

Timing, Threshold, and Duration of Intraoperative Hypotension in Cardiac Surgery: Their Associations With Postoperative Delirium.

OBJECTIVES: To study the timing, threshold, and duration of intraoperative hypotension (IOH) associated with the risk of postoperative delirium (POD). DESIGN: A single-center retrospective observational study. SETTING: University teaching hospital. PARTICIPANTS: A total of 503 adult patients who underwent cardiac valvular surgery that required cardiopulmonary bypass (CPB). MEASUREMENTS AND MAIN RESULTS: The authors predefined the following 4 periods: (1) during surgery, (2) pre-CPB, (3) during CPB, and (4) post-CPB, and 8 thresholds of mean arterial pressure for IOH according to every 5 mmHg between 50 mmHg and 85 mmHg. The authors calculated the cumulative duration below the 8 thresholds in each period. The primary outcome was delirium defined as a score of ≥4 for at least one Intensive Care Delirium Screening Checklist assessment during 48 h after the surgery. Among 503 patients, POD occurred in 95 patients (18.9%). There was no significant association of POD with all of the thresholds of IOH in the periods of pre-CPB, during CPB, and during surgery. However, in the post-CPB period, the patients with POD had a significantly longer cumulative duration of IOH according to all of the thresholds of mean arterial pressure. In multivariate analyses, 4 IOH thresholds in the post-CPB period were associated independently with POD: <60 mmHg (odds ratio [OR] =1.84 [95% CI 1.10-3.10]), <65 mmHg (OR = 1.72 [1.01-2.92]), <70 mmHg (OR = 1.83 [1.03-3.26]), and <75 mmHg (OR = 1.94 [1.02-3.69]). CONCLUSIONS: A longer cumulative duration of IOH with the threshold between <60 and <75 mmHg that occurred after CPB was independently associated with the risk of POD.

Perioperative Serum Free Hemoglobin and Haptoglobin Levels in Valvular and Aortic Surgery With Cardiopulmonary Bypass: Their Associations With Postoperative Kidney Injury.

OBJECTIVE: To observe the perioperative free hemoglobin and haptoglobin levels and to assess their associations with the risk of postoperative acute kidney injury (pAKI) in adult patients undergoing valvular and aortic surgery requiring cardiopulmonary bypass (CPB). DESIGN: A single-center, prospective, observational study. SETTING: Public teaching hospital. PARTICIPANTS: The study comprised 74 adult patients without chronic renal failure who underwent cardiovascular surgery requiring CPB from 2014 to 2020. MEASUREMENTS AND MAIN RESULTS: Perioperative free hemoglobin and haptoglobin levels during the study period were obtained from study participants. The primary outcome was pAKI defined by the Kidney Disease: Improving Global Outcomes criteria. Of the 74 patients in this study, pAKI occurred in 25 patients (33.8%). The free hemoglobin level began to increase after the initiation of CPB and reached a peak level at 30 minutes after weaning from CPB. It returned to the baseline level on postoperative day one. Haptoglobin levels were the highest after anesthesia induction and decreased continuously until postoperative day one. In the multivariate analysis, maximum free hemoglobin and minimum haptoglobin were associated independently with increased risk of pAKI (adjusted odds ratio 1.33 [95% confidence interval 1.12-1.58; p = 0.001] and 0.95 [95% confidence interval 0.91-1.00; p = 0.03], respectively). The free hemoglobin level began to have an independent association with pAKI at one hour after commencement of CPB, and the independent association disappeared at postoperative day one. CONCLUSIONS: This study found that the perioperative increase of the free hemoglobin level and the decrease of the haptoglobin level had independent associations with the risk of pAKI.

Abdominal compartment syndrome in a monochorionic-triamniotic triplet pregnancy complicated by feto-fetal transfusion syndrome.

A 40-year-old primigravida woman with a monochorionic-triamniotic (MT) triplet pregnancy was hospitalized due to threatened abortion at 16 gestational weeks. Polyhydramnios in two fetuses and oligohydramnios in the third supported a diagnosis of feto-fetal transfusion syndrome (FFTS) at 23 weeks and 3 days of gestation. Severe dyspnea and liver dysfunction required intensive care unit admission and mechanical ventilation support, and abdominal compartment syndrome (ACS) caused by polyhydramnios was clinically diagnosed. When her general condition was not improved regardless of intensive care, the patient delivered the three fetuses by cesarean section at 23 weeks and 5 days gestation. Abdominal decompression was achieved with delivery, and the patient was discharged 13 days after operation without morbidity. This is the first case report of ACS caused by FFTS in a MT triplet pregnancy resulting in extremely preterm birth.

Suppression of behavioral activity and hippocampal noradrenaline caused by surgical stress in type 2 diabetes model mice.

BACKGROUND: There has been much discussion recently about the occurrence of neuropsychological complications during the perioperative period. Diabetes is known to be one of the metabolic risk factors. Although the number of patients with diabetes mellitus (DM) has been increasing, the pathophysiology of postoperative neuropsychological dysfunction in DM patients is still unclear. Recently, a deficiency of neurotransmitters, such as monoamines, was reported to be associated with mental disorders. Therefore, we investigated the effects of surgical stress on behavioral activity and hippocampal noradrenaline (NA) level in type 2 diabetes mellitus model (T2DM) mice. METHODS: Eighty-four 6-week-old male C57BL/6J mice were divided into four groups (non-diabetes, non-diabetes with surgery, T2DM, and T2DM with surgery groups). T2DM mice were established by feeding a high-fat diet (HFD) for 8 weeks. At 14 weeks of age, fifteen mice in each group underwent a series of behavioral tests including an open field (OF) test, a novel object recognition (NOR) test and a light-dark (LD) test. In the surgery groups, open abdominal surgery with manipulation of the intestine was performed 24 h before the behavioral tests as a surgical stress. Hippocampal noradrenaline (NA) concentration was examined in six mice in each group by high-performance liquid chromatography. The data were analyzed by the Mann-Whitney U test, and p values less than 0.05 were considered significant. RESULTS: The T2DM group showed significantly increased explorative activity in the NOR test (P = 0.0016) and significantly increased frequency of transition in the LD test (P = 0.043) compared with those in the non-diabetic group before surgery. In T2DM mice, surgical stress resulted in decreased total distance in the OF test, decreased explorative activity in the NOR test, and decreased frequency of transition in the LD test (OF: P = 0.015, NOR: P = 0.009, LD: P = 0.007) and decreased hippocampal NA (P = 0.015), but such differences were not observed in the non-diabetic mice. CONCLUSIONS: Mice with T2DM induced by feeding an HFD showed increased behavioral activities, and surgical stress in T2DM mice caused postoperative hypoactivity and reduction of the hippocampal NA level.

Long-term preoperative glycemic control restored the perioperative neutrophilic phagocytosis activity in diabetic mice.

BACKGROUND: The risk of surgical site infection has been reported to be higher in patients with poorly controlled diabetes. Since chronic hyperglycemia impairs neutrophil functions, preoperative glycemic control may restore neutrophil function. However, long-term insulin therapy may lead to a delay in surgery, which may be a problem, especially in cancer surgery. It is therefore unfortunate that there have been few studies in which the optimal duration of perioperative glycemic control for diabetes with chronic hyperglycemia was investigated. Therefore, we investigated the effects of preoperative long-term insulin therapy and short-term insulin therapy on perioperative neutrophil functions in diabetic mice with chronic hyperglycemia. METHODS: Five-week-old male C57BL/6 J mice were divided into four groups (No insulin (Diabetes Mellitus: DM), Short-term insulin (DM), Long-term insulin (DM), and Non-diabetic groups). Diabetes was established by administrating repeated low-dose streptozotocin. The Short-term insulin (DM) group received insulin therapy for 6 h before the operation and the Long-term insulin (DM) group received insulin therapy for 5 days before the operation. The No insulin (DM) group and the Non-diabetic group did not receive insulin therapy. At 14 weeks of age, abdominal surgery with intestinal manipulation was performed in all four groups. We carried out a phagocytosis assay with fluorescent microspheres and a reactive oxygen species (ROS) production assay with DCFH-DA (2',7'-dichlorodihydrofluorescein diacetate) before and 24 h after the operation using FACSVerse™ with BD FACSuite™ software. RESULTS: Blood glucose was lowered by insulin therapy in the Short-term insulin (DM) and Long-term insulin (DM) groups before the operation. Neutrophilic phagocytosis activities before and after the operation were significantly restored in the Long-term insulin (DM) group compared with those in the No insulin (DM) group (before: p = 0.0008, after: p = 0.0005). However, they were not significantly restored in the Short-term insulin (DM) group. Neutrophilic ROS production activities before and after the operation were not restored in either the Short-term insulin (DM) group or Long-term insulin (DM) group. CONCLUSIONS: Preoperative and postoperative phagocytosis activities are restored by insulin therapy for 5 days before the operation but not by insulin therapy for 6 h before the operation.

The association of intraoperative end-tidal carbon dioxide with the risk of postoperative nausea and vomiting.

PURPOSE: Patients undergoing gynecological surgery are considered to be a high-risk cohort for postoperative nausea and vomiting (PONV). The purpose of this study was to assess the association of intraoperative end-tidal carbon dioxide (EtCO2) with risk of PONV in patients underwent gynecological open surgery. METHODS: In this single-center retrospective observational study, we included patients aged 20-60 years who underwent elective gynecological open surgery. We obtained data for the incidence of PONV within 24 h after operation. We collected EtCO2 every minute during the operation, and determined the lowest value of EtCO2. We compared the lowest EtCO2 between patients with and without PONV. Multivariate logistic regression analysis was performed to assess the independent association of EtCO2 with the risk of PONV. RESULTS: A total of 146 patients were included in the current study. There were 81 patients with PONV within 24 h after the operation. The median lowest value of EtCO2 in patients with PONV was significantly lower than that in patients without PONV (31 vs 33 mmHg, p = 0.02). In the multivariate logistic regression model, we found that lowest EtCO2 ≤ 31 mmHg was independently associated with increase in the risk of PONV (adjusted odds ratio = 3.37, p = 0.02). CONCLUSION: In this retrospective observational study, low intraoperative EtCO2 was shown to be independently associated with increased risk of PONV. However, this result may be skewed by uncollected information including previous PONV, motion sickness or other unknown bias, so future studies should be conducted to refute or confirm our findings.

Influence of Nutritional Management and Rehabilitation on Physical Outcome in Japanese Intensive Care Unit Patients: A Multicenter Observational Study.

BACKGROUND: There is lack of evidence regarding nutritional management among intensive care unit (ICU) patients in a population with relatively low body mass index. Therefore, we conducted an observational study to assess the nutritional management in Japanese ICUs. Also, we investigated the impact of nutritional management and rehabilitation on physical outcome. METHODS: The study population comprised 389 consecutive patients who received mechanical ventilation for at least 24 h and those admitted to the ICU for > 72 h in 13 hospitals. The primary outcomes were caloric and protein intake in ICU on days 3 and 7, and at ICU discharge. The secondary outcome was the impact of nutritional management and rehabilitation on physical status at ICU discharge. We defined good physical status as more than end sitting and poor physical status as bed rest and sitting. We divided the participants into 2 groups, namely, the good physical status group (Good group) and poor physical status group (Poor group) for analysis of the secondary outcome. Data were expressed as median (interquartile range). RESULTS: The median amount of caloric intake on days 3 and 7, and at ICU discharge via enteral and parenteral routes were 8.4 (3.1-15.6), 14.9 (7.5-22.0), and 11.2 (2.5-19.1) kcal/kg/day, respectively. The median amount of protein intake on days 3 and 7, and at ICU discharge were 0.2 (0-0.5), 0.4 (0.1-0.8), and 0.3 (0-0.7) g/kg/day, respectively. The amount of caloric intake on day 3 in the Poor group was significantly higher than that of the Good group (10.1 [5.8, 16.2] vs. 5.2 [1.9, 12.4] kcal/kg/day, p < 0.001). The proportion of patients who were received rehabilitation in ICU in the Good group was significantly higher than that of the Poor group (92 vs. 63%, p < 0.001). The multivariate analysis revealed that caloric intake on day 3 and rehabilitation in ICU were considered independent factors that affect physical status (OR 1.19; 95% CI 1.05-1.34; p = 0.005 and OR 0.07; 95% CI 0.01-0.34; p = 0.001). CONCLUSIONS: The caloric and protein intakes in Japanese ICUs were 15 kcal/kg/day and 0.4 g/kg/day, respectively. In addition, critically ill patients might benefit from low caloric intake (less than 10 kcal/kg/day) until day 3 and rehabilitation during ICU stay.

The impact of intravenous isotonic and hypotonic maintenance fluid on the risk of delirium in adult postoperative patients: retrospective before-after observational study.

PURPOSE: To assess the impact of intravenous isotonic and hypotonic maintenance fluid on the risk of delirium in adult postoperative patients, we conducted retrospective before-after study in a tertiary teaching hospital. METHODS: We examined all adult patients admitted ICU after an elective operation for head and neck cancer, or esophageal cancer from February 2014 to January 2017. From February 2014 to July 2015, patients were administered hypotonic fluid (sodium; 35 mmol/L) as the National Institute for Health and Care Excellence (NICE) have recommended. From August 2015 to January 2017, patients were administered isotonic fluid (sodium; 140 mmol/L). We defined the incidence of delirium as the primary outcome. The delirium was defined as the Intensive Care Delirium Screening Checklist during the ICU stay ≥ 4. A propensity score-matched model was used to adjust confounders. RESULTS: As postoperative intravenous maintenance fluid, hypotonic fluid was administered to 119 patients and isotonic fluid was administered to 92 patients. Among those total cohorts, the incidence of postoperative delirium in the hypotonic group was 21.8%, which was significantly higher than that (9.8%) in the isotonic group (p = 0.019). After propensity score matching, we selected 77 patients in each group. The incidence of delirium during the ICU stay in the hypotonic group was 26.0%, which was significantly higher than the incidence of 11.7% in the isotonic group (p = 0.023). CONCLUSIONS: In this study, the use of postoperative hypotonic maintenance fluid was associated with a higher risk of postoperative delirium than that when isotonic maintenance fluid was used.

Glycated hemoglobin A1c level on the day of emergency surgery is a marker of premorbid glycemic control: a retrospective observational study.

BACKGROUND: Current international guideline recommends to maintain blood glucose level ≤ 180 mg/dL in acute ill patients, irrespective of presence of premorbid diabetes. However, there are studies suggested that optimal acute glycemic control should be adjusted according to premorbid glycemic control in patients with chronic hyperglycemia. Accordingly, to obtain the information of premorbid glycemic control would be relevant. However, the HbA1c level on the day of the emergency operation (HbA1c-ope) might not be useful as a surrogate of premorbid chronic glycemic control, since glucose metabolism can be affected by inflammation, severity of illness and surgical invasion. METHODS: We hypothesized that HbA1c-ope reflects pre-morbid glycemic control. To assess this hypothesis, we conducted a single-center retrospective observational study to assess the association between HbA1c-ope and HbA1c level measured within 30 days before the operation (HbA1c-pre). We screened patients who had been admitted to the ICU of our hospital after emergency surgery during the period from January 2008 to December 2016. Patients in whom both of HbA1c-ope and HbA1c-pre were measured were included in this study. We compared HbA1c-ope and HbA1c-pre using the paired t-test. The correlation between the two HbA1c measurements was assessed using Pearson's correlation coefficient. Its agreement was assessed using the Bland-Altman approach with 95% confidence intervals. RESULTS: We included 48 patients in this study. The mean value of HbA1c-pre was 6.3%, which was not significantly different from the mean value of 6.2% for HbA1c-ope (p = 0.12). There was a significant correlation between HbA1c-pre and HbA1c-ope (r2 = 0.70, p < 0.001). The mean difference between two HbA1c measurements was 0.12% (95% CI: -0.03% to 0.27%). The limit of agreement ranged from - 0.9% to +1.1%. CONCLUSIONS: We found that there was a significant correlation between HbA1c-ope and HbA1c-pre. Our findings suggest that HbA1c-ope can be used to estimate previous glycemic control with an acceptable degree of accuracy, enabling personalized glycemic control in the perioperative period.

Haptoglobin Administration in Cardiovascular Surgery Patients: Its Association With the Risk of Postoperative Acute Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) often occurs after cardiac surgery. During cardiac surgery, plasma free hemoglobin (fHb) would increase due to hemolysis. Since plasma fHb is thought to be nephrotoxic, haptoglobin, which is an fHb scavenger, may have the potential to prevent postoperative AKI (pAKI). However, there have been few studies in which the association of intraoperative administration of haptoglobin with the incidence of AKI after cardiac surgery was assessed. METHODS: This study was a retrospective observational study to assess the independent association of intraoperative administration of haptoglobin with the incidence pAKI in cardiac surgery patients. We screened cardiac surgery patients who required cardiopulmonary bypass from 2008 to 2015. We excluded patients who required renal replacement therapy preoperatively. We also excluded patients in whom descending aortic replacement was performed. pAKI was defined according to AKI Network criteria. A propensity score-matched model was used to adjust confounders. For sensitive analysis, we further developed a logistic regression model. RESULTS: We included 1326 patients in this study. The incidence of AKI in the total cohort was 25.5% (338 patients). Haptoglobin was administered in 260 patients (19.6%). In the crude cohort, the incidence of AKI in patients with haptoglobin administration was 24.6%, which was not significantly different from the incidence of 25.7% in those without haptoglobin administration (P = .72; odds ratio, 0.94 [95% confidence interval, 0.69-1.29]). After propensity score matching, we had 249 patients in each group (for a total of 498 patients). In this propensity score-matched cohort, the incidence of AKI in patients with haptoglobin administration was 22.5%, which was significantly lower than the incidence of 30.9% in those without haptoglobin administration (P = .033; odds ratio, 0.65 [0.43-0.97]). In our logistic regression model for the risk of pAKI, haptoglobin administration was independently associated with decreased risk of AKI (P = .029; adjusted odds ratio, 0.54 [0.31, 0.93]). CONCLUSIONS: In this hypothesis-generating, single-center retrospective observational study, intraoperative administration of haptoglobin was independently associated with lower risk of AKI after cardiovascular surgery.

Perioperative Brain Natriuretic Peptide in Pediatric Cardiac Surgery Patients: Its Association With Postoperative Outcomes.

OBJECTIVES: The aim of this study was to investigate the relationship between perioperative brain natriuretic peptide levels and the incidence of postoperative serious adverse events (SAEs) in pediatric cardiac patients. DESIGN: A prospective observational study. SETTING: A single-institution university hospital. PARTICIPANTS: Children under 15 years old who underwent cardiac surgery that required cardiopulmonary bypass from December 21, 2012 to February 26, 2014. The Risk Adjustment for Congenital Heart Surgery 1 category less than 1 was excluded. INTERVENTIONS: Brain natriuretic peptide (BNP) levels were measured preoperatively (BNPpre) and on postoperative day 1 (BNPPOD1) and postoperative day 3 (BNPPOD3). METHODS AND RESULTS: Primary outcome was the incidence of postoperative SAEs; (1) death in the intensive care unit, (2) requirement of extracorporeal membrane oxygenation, (3) cardiac arrest, and (4) requirement of reoperation for hemodynamic instability. The authors included 71 patients in this study. There were 8 patients (11%) who had at least 1 SAE. Median preoperative BNP level in patients with SAEs was significantly higher than in those without SAEs (1,541 pg/mL [IQR: 121-5,962] v 122 pg/mL [QR: 34-342], p = 0.01). From the receiver operating characteristic curve of BNPpre for the incidence of SAEs, an area under the curve was 0.77 (95%CI 0.55-0.91). The best cutoff BNPpre number was 1,000 pg/mL. From the multivariate logistic regression model, BNPpre>1,000 pg/mL was associated independently with risk of SAEs (adjusted odds ratio = 8.5, 95% CI [1.3, 59.3], p = 0.02). CONCLUSIONS: In conclusion, the authors' study showed that increased preoperative brain natriuretic peptide concentration, especially a concentration of more than 1,000 pg/mL, was associated with risk of SAEs in pediatric cardiac surgery patients.

Constant Current vs. Constant Voltage Systems for Temporal Spinal Cord Stimulation for Intractable Pain.

Although spinal cord stimulation (SCS) is a useful treatment for chronic intractable pain, the optimal method of stimulation has not yet been established. In this prospective, crossover study, we compared the efficacy of using a constant current (CC) system with that of a constant voltage (CV) system for temporal SCS. Twenty patients were enrolled and divided into two groups. For 10 patients, a CV system was applied on Days 1-5, followed by the use of a CC system on Days 6-10. For the other 10 patients, a CC system was applied for the first five days, followed by a CV system for the subsequent five days. We evaluated the alteration of pain intensity using a visual analogue scale (VAS), the area of stimulation, the stability of effect, and patient satisfaction regarding treatment. The pain scores decreased significantly after the start of the SCS. There was no significant difference in the change in VAS between the two systems. The stimulation method used for temporal SCS did not affect the reduction of pain intensity. Patients felt a wider stimulation area by the CC system compared to the CV system.

Comparison of the incidences of hyponatremia in adult postoperative critically ill patients receiving intravenous maintenance fluids with 140 mmol/L or 35 mmol/L of sodium: retrospective before/after observational study.

PURPOSE: The purpose of this study was to compare the incidences of hyponatremia in adult postoperative critically ill patients receiving isotonic and hypotonic maintenance fluids. METHODS: In this single-center retrospective before/after observational study, we included patients who had undergone an elective operation for esophageal cancer or for head and neck cancer and who received postoperative intensive care for >48 h from August 2014 to July 2016. In those patients, sodium-poor solution (35 mmol/L of sodium; Na35) had been administered as maintenance fluid until July 2015. From August 2015, the protocol for postoperative maintenance fluid was revised to the use of isotonic fluid (140 mmol/L of sodium; Na140). The primary outcome was the incidence of hyponatremia (<135 mmol/L) until the morning of postoperative day (POD) 2. RESULTS: We included 179 patients (Na35: 87 patients, Na140: 92 patients) in the current study. The mean volume of fluid received from ICU admission to POD 2 was not significantly different between the two groups (3291 vs 3337 mL, p = 0.84). The incidence of postoperative hyponatremia was 16.3% (15/92) in the Na140 cohort, which was significantly lower than that of 52.9% (46/87) in the Na35 group (odds ratio = 0.17, 95% confidence interval 0.09-0.35, p < 0.001]. The incidences of hypernatremia, defined as serum sodium concentration >145 mmol/L, were not significantly different between the two groups. CONCLUSION: In this study, the use of intravenous maintenance fluid with 35 mmol/L of sodium was significantly associated with an increased risk of hyponatremia compared to that with 140 mmol/L of sodium in adult postoperative critically ill patients.

Storage duration of transfused red blood cells is not significantly associated with postoperative adverse events in pediatric cardiac surgery patients.

The aim of this study was to evaluate the association of storage duration of transfused red blood cells with the risk of postoperative serious adverse events in pediatric cardiac surgery patients. We studied 517 patients and found that 22 patients (4.3%) had at least one serious adverse event. The maximum and mean storage duration of transfused red blood cells did not differ significantly between patients with and without serious adverse events (maximum, p = 0.89; mean, p = 0.81). In our study of pediatric cardiac surgery patients, the storage duration of transfused red blood cells was not significantly associated with the risk of serious adverse events.