Hui Liu

Vasopressors in septic shock: a systematic review and network meta-analysis

Objective Vasopressor agents are often prescribed in septic shock. However, their effects remain controversial. We conducted a systematic review and Bayesian network meta-analysis to compare the effects among different types of vasopressor agents. Data sources We searched for relevant studies in PubMed, Embase, and the Cochrane Library databases from database inception until December 2014. Study selection Randomized controlled trials in adults with septic shock that evaluated different vasopressor agents were selected. Data extraction Two authors independently selected studies and extracted data on study characteristics, methods, and outcomes. Data synthesis Twenty-one trials (n=3,819) met inclusion criteria, which compared eleven vasopressor agents or vasopressor combinations (norepinephrine [NE], dopamine [DA], vasopressin [VP], epinephrine [EN], terlipressin [TP], phenylephrine [PE], TP+NE, TP + dobutamine [DB], NE+DB, NE+EN, and NE + dopexamine [DX]). Except for the superiority of NE over DA, the mortality of patients treated with any vasopressor agent or vasopressor combination was not significantly different. Compared to DA, NE was found to be associated with decreased cardiac adverse events, heart rate (standardized mean difference [SMD]: −2.10; 95% confidence interval [CI]: −3.95, −0.25; P=0.03), and cardiac index (SMD: −0.73; 95% CI: −1.14, −0.03; P=0.004) and increased systemic vascular resistance index (SVRI) (SMD: 1.03; 95% CI: 0.61, 1.45; P<0.0001). This Bayesian meta-analysis revealed a possible rank of probability of mortality among the eleven vasopressor agents or vasopressor combinations; from lowest to highest, they are NE+DB, EN, TP, NE+EN, TP+NE, VP, TP+DB, NE, PE, NE+DX, and DA. Conclusion In terms of survival, NE may be superior to DA. Otherwise, there is insufficient evidence to suggest that any other vasopressor agent or vasopressor combination is superior to another. When compared to DA, NE is associated with decreased heart rate, cardiac index, and cardiovascular adverse events, as well as increased SVRI. The effects of vasopressor agents or vasopressor combinations on mortality in patients with septic shock require further investigation.

Effects of continuous venous-venous hemofiltration on heat stroke patients: a retrospective study.

BACKGROUND Heat stroke (HS) is a fatal illness characterized by an elevated core body temperature above 40°C and complicated with rhabdomyolysis and acute renal failure. We retrospectively analyzed the effect of continuous veno-venous hemofiltration (CVVH) in patients with HS. METHODS A total of 16 patients with HS were retrospectively analyzed. All patients were treated by CVVH for at least 96 hours, and CVVH was initiated with replacement fluid between 25°C and 30°C for 2 hours to 2.5 hours, and 36°C thereafter. The vital signs were monitored and blood samples were collected during CVVH to measure serum urea, creatinine, myoglobin, creatine kinase, and total bilirubin. RESULTS All patients survived. The core temperature of the patients decreased from 41.3 ± 0.2°C to 38.7 ± 0.1°C after 2 hours and to 36.7 ± 0.1°C after 5 hours during CVVH (p < 0.05). Compared with values before starting CVVH, there were remarkable improvements in mean arterial blood pressure, heart rate, and oxygenation index (p < 0.05). The serum creatinine, urea, myoglobin, and creatine kinase decreased significantly (p < 0.05), while the bilirubinemia had no obvious decline (p > 0.05). The scores of APACHE II and arterial lactate had also obvious decline (p < 0.05). The hemodynamic variables were stabilized during CVVH, and no obvious side effects related to CVVH were found. CONCLUSIONS CVVH is safe and feasible in the treatment of patients with HS by lowering core temperature, removal of myoglobin, support of multiorgan function, and modulating systemic inflammatory response syndrome (SIRS). The impact of CVVH on patient outcome, however, still needs proof by larger randomized controlled trials.

The diagnostic accuracy of urinary [timp-2]·[igfbp7] for acute kidney injury in adults: A Prisma-compliant meta-analysis

Introduction: Early diagnosis of acute kidney injury (AKI) remains a challenge. Recently, [TIMP-2]·[IGFBP7], which is a combination of urine tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor (IGF) binding protein 7 (IGFBP7), has been identified as a potential biomarker of AKI. We performed this meta-analysis to assess the diagnostic accuracy of urinary [TIMP-2]·[IGFBP7] for AKI in adult patients. Methods: We searched the PubMed, Embase, and Cochrane Library databases from database inception to March 2017. Two authors independently screened articles based on inclusion and exclusion criteria and assessed the methodological quality of each included study using the Quality Assessment of Diagnostic Accuracy Studies 2 criteria. Review Manager and STATA were used for all statistical analyses. Results: Nine studies (n = 1886) satisfied the inclusion criteria. Pooled analyses demonstrated that urinary [TIMP-2]·[IGFBP7] exhibited fair diagnostic accuracy for AKI (sensitivity [SEN] 0.83 [95% CI 0.75–0.89], specificity [SPE] 0.72 [95% CI 0.56–0.84], and area under the summary receiver operating characteristic [SROC] curve 0.86 [95% CI 0.82–0.88]) and AKI stage ≥ 2 (according to the 2012 Kidney Disease: Improving Global Outcomes [KDIGO] 2012 classification system; SEN 0.92 [95% CI 0.81–0.96], SPE 0.63 [95% CI 0.49–0.74], and area under the SROC curve 0.88 [95% CI 0.85–0.91]) in adult patients. Conclusion: Our findings indicate that urinary [TIMP-2]·[IGFBP7] may be a reliable biomarker for the early detection of AKI. However, given the significant heterogeneity among the included studies, clinicians should be aware of the utility and limitations of this biomarker in clinical practice. Additional high-quality studies examining a larger sample of patients are required.

Acute kidney injury and inflammatory response of sepsis following cecal ligation and puncture in D-galactose-induced aging rats

Background Recently, the d-galactose (d-gal)-induced mimetic aging rat model has been widely used in studies of age-associated diseases, which have shown that chronic d-gal exposure induces premature aging similar to natural aging in rats. With the increasing rate of sepsis in the geriatric population, an easy-access animal model for preclinical studies of elderly sepsis is urgently needed. This study investigates whether a sepsis model that is established in d-gal-induced aging rats can serve as a suitable model for preclinical studies of elderly patients with sepsis. Objective To investigate the acute kidney injury (AKI) and inflammatory response of sepsis following cecal ligation and puncture (CLP) in d-gal-induced aging rats. Methods Twelve-week-old male Sprague Dawley rats were divided into low-dose d-gal (L d-gal, 125 mg/kg/d), high-dose d-gal (H d-gal, 500 mg/kg/d), and control groups. After daily subcutaneous injection of d-gal for 6 weeks, the CLP method was used to establish a sepsis model. Results The mortality was 73.3%, 40%, and 33.3% in the H d-gal, L d-gal, and control groups, respectively. Blood urea nitrogen, creatinine, plasma neutrophil gelatinase-associated lipocalin, interleukin-6, interleukin-10, and tumor necrosis factor-α were markedly increased in the H d-gal group after establishment of the sepsis model (H d-gal vs control, P<0.05 at 12 h and 24 h post-CLP). The rate of severe AKI (RIFLE-F) at 24 h post-CLP was 43% for both the control and L d-gal groups and 80% for the H d-gal group. Conclusion High-dose- d-gal-induced aging rats are more likely to die from sepsis than are young rats, and probably this is associated with increased severity of septic AKI and an increased inflammatory response. Therefore, use of the high-dose- d-gal-induced aging rat model of sepsis for preclinical studies can provide more useful information for the treatment of sepsis in elderly patients.

Analysis of risk factors affecting prognosis of exertional heat stroke

OBJECTIVE To determine prognostic risk factors of exertional heat stroke (EHS). METHODS Sixty-nine patients who met the case definition of EHS at ten military hospitals from June 2002 to August 2012 were enrolled in this retrospective study. The clinical data and prognosis was observed, including rhabdomyolysis (RM), disseminated intravascular coagulation (DIC), acute kidney injury (AKI), hepatosis, epilepsy, shock, arrhythmia, multiple organ dysfunction syndrome (MODS) and consciousness disorder. A logistic regression analysis was made to look for the significant risk factors, and its accuracy and reliability were tested and verified by statistical equation. RESULTS There were 69 patients with EHS in the study, and 18 (26.09%) were dead. The independent prognostic factors were identified as DIC and AKI [DIC odds ratio (OR)=94.994, 95% confidence interval (95%CI) 3.837-2352.031, P=0.005; AKI OR=90.871, 95%CI 2.079-3971.995, P=0.019]. The mortality was 16.67% (3/18) when any one factor exist; the mortality was 93.75% (15/16) when two factors exist (sensibility was 83.33%; with specificity of 98.03%, positive predictive value of 93.75%, negative predictive value of 94.34%, and accuracy of 94.20%). CONCLUSIONS Among all the clinical parameters, the major risk factors affecting prognosis of EHS included DIC and AKI. The mortality might go very high if both two risk factors exist.

Efficacy and safety of daptomycin for skin and soft tissue infections: a systematic review with trial sequential analysis

Background Skin and soft tissue infections (SSTIs) are significant indications for antibiotic treatment. Daptomycin, a novel antibiotic, has been registered and licensed to be used in the treatment of these infections. However, its efficacy and safety remain controversial. Objective The objective of this study was to conduct a systematic review with trial sequential analysis (TSA) to evaluate the efficacy and safety of daptomycin for the treatment of SSTIs and to analyze whether the available sample size has been large enough and is conclusive. Methods PubMed, the Cochrane Library, and EMBASE were searched for published randomized controlled trials (RCTs) that compared daptomycin with other antibiotics in adult patients with SSTIs up to February 2016. Results This meta-analysis included eight randomized controlled trials (n=2,002). There was no difference in either the clinical success rate (intention-to-treat population: relative risk [RR] =1.04, 95% confidence interval [CI] =0.99–1.10, P=0.12; clinically evaluable population: RR =1.00, 95% CI =0.97–1.04, P=0.82) or the microbiological success rate (RR =1.00, 95% CI =0.95–1.06, P=0.92) between the daptomycin and comparator groups for treating SSTIs, which was confirmed by TSA. Compared with vancomycin, daptomycin exhibited no advantage in increasing the clinical success rate (RR =1.03, 95% CI =0.95–1.13, P=0.47), and this was also confirmed by TSA. All-cause mortality, overall treatment-related adverse events, and creatine phosphokinase events were similar between these two groups. Conclusion Daptomycin and comparator drugs are equally efficacious with regard to clinical and microbiological success for patients with SSTIs, and TSA showed that no additional randomized controlled trials are required. Although daptomycin is a good alternative when other antibiotics are contraindicated for patients with SSTIs and it can serve as a first-line treatment for SSTIs, clinicians should be aware of potential adverse events, such as daptomycin-induced acute eosinophilic pneumonia and creatine phosphokinase, when treating patients with daptomycin.

[Clinical study of prognostic value of interleukin-6 in severe acute pancreatitis].

OBJECTIVE To investigate the value of serum interleukin-6 (IL-6) level as a prognostic indicator in severe acute pancreatitis (SAP) patients. METHODS Data of 62 cases of SAP admitted to Department of Critical Care Medicine from January 2006 to September 2012 were retrospectively analyzed. They were divided into two groups: non-survivor group (n=15) and survivor group (n=47). Serum levels of IL-6 at 24, 48, 72 hours after admission were compared between two groups. Correlation between IL-6 value and acute physiology and chronic health evaluation II (APACHE II) score and CT severity index (CTSI) at 48 hours were analyzed. The receiver-operating characteristic curve (ROC curve) was plotted at 48 hours to analyze the accuracy of IL-6 value as a prognostic indicator in the initial stage of SAP. RESULTS The IL-6 values were elevated obviously followed by a lowering in non-survivor group. However, it continued to decrease gradually in survivor group. The IL-6 values of non-survivor group were significantly higher than those of survivor group at 48 hours and 72 hours after admission (545.5 ± 265.7 ng/L vs. 147.2 ± 107.0 ng/L, 243.0 ± 133.6 ng/L vs. 119.0 ± 69.5 ng/L, both P<0.01). IL-6 ROC had an area under curve (AUC) of 0.930 at 48 hours. In both groups, IL-6 values and APACHEII score showed a positive correlation (r=0.930, P=0.003; r=0.964, P=0.000), and also between IL-6 values and CTSI (r=0.915, P=0.000; r=0.921, P=0.005) at 48 hours. CONCLUSION IL-6 can be a useful indicator of the prognosis in the initial stage of SAP (48 hours).

1373: EFFICACY OF CONTINUOUS BLOOD PURIFICATION ON PATIENTS WITH HYPERLIPIDEMIC SEVERE ACUTE PANCREATITIS

www.ccmjournal.org Critical Care Medicine • Volume 46 • Number 1 (Supplement) Learning Objectives: Ingestion of toxic alcohols (TA) typically presents with a high anion gap metabolic acidosis, and elevated osmolar gap. TA levels are measured by gas chromatography, a technique not commonly performed on-site in hospital laboratories. Therefore, in the absence of this information, clinical suspicion and classic metabolic derangements guide therapy. Hemodialysis (HD) has been used to remove alcohols and its metabolites. However, early HD has not been recommended in early phases of intoxication with high osmolar gap (OG) and normal anion gap (AG) metabolic acidosis. Methods: 40-year-old male was brought to our emergency department for reported paint thinner ingestion. He was emergently intubated. Blood gas showed respiratory acidosis. The initial AG was 11, and lactic acid 5.26 mmol/L. Measured and calculated serum osmolality was 454 mosm/kg and 284 mosm/kg, respectively with the OG of 170. Patient was treated with bicarbonate drip, fomepizole and emergent HD. Measured serum osmolality and serum creatinine after HD was 314 mosm/kg and 0.71 mg/dL. Patient was extubated did well. Right before discharge, serum ethylene glycol and methanol level (16 hours into admission) resulted as 351 mg/dL and 865 mg/mL. Serum ethanol, acetone, and isopropyl were not detected. We later found out that he actually ingested 3 solutions: paint thinner (turpentine), antifreeze coolant (ethylene glycol plus diethylene glycol), and windshield washer fluid (methanol). Results: Most of the TA are metabolized into their toxic byproducts by the enzyme alcohol dehydrogenase. The half life of these substances is determined by their own kinetics and the ingestion of multiple elements that can compete for the enzyme. The half life of methanol is 14 – 30 hrs, while ethylene glycol is 3 -8 hrs. An early presentation after the ingestion will not give enough time for these toxic alcohols to be metabolized, translating in a high OG without a high AG. False elevation lactate can occur with ingestion of ethylene glycol due to its metabolites crossreacting with L-lactate oxidase in the blood gas analyzer. In our case, the administration of fomepizole followed by an early HD given the poor improvement in the OG with supportive treatment was followed by a fast recovery of the neurological status of the patient and potentially prevented renal failure. A particularly high index of suspicion for TA ingestion should be raised when encountering an individual with lactic acid elevation, high OG, and normal AG.

Correlation between gastrointestinal dysfunction and both severity and prognosis in patients suffering from heatstroke

OBJECTIVE To investigate the relationship between gastrointestinal dysfunction and both severity and prognosis in patients with heatstroke ( HS ). METHODS A retrospective analysis was conducted. Clinical data from 39 patients with HS seeking for treatment in Department of Critical Care Medicine of Chinese PLA General Hospital from January 2013 to September 2014 were enrolled. The patients were divided into two groups: gastrointestinal dysfunction group and non-gastrointestinal dysfunction group. The acute physiology and chronic health evaluation II ( APACHEII) score within 24 hours of admission and 28-day mortality were compared between two groups. In gastrointestinal dysfunction group, the gastrointestinal dysfunction score, the duration days of gastrointestinal dysfunction, the length of intensive care unit ( ICU ) stay, and the duration of mechanical ventilation were collected. Pearson correlation analysis was used to analyze the relationship between gastrointestinal function and the severity of the ailment as well as the prognosis. RESULTS Among 39 patients with HS, 32 of them showed gastrointestinal dysfunction with an incidence of 82.05%. In gastrointestinal dysfunction group, the gastrointestinal dysfunction score was 2.3±0.8, the duration of gastrointestinal dysfunction was ( 17.3±15.2 ) days, the length of ICU stay was ( 37.8±25.0 ) days, and the duration of mechanical ventilation was ( 27.8±14.0 ) days. APACHEII score in gastrointestinal dysfunction group was significantly higher than that of the non-gastrointestinal dysfunction group ( 26.30±6.00 vs. 17.40±6.00, t = 3.555, P = 0.001 ). The 28-day mortality in gastrointestinal dysfunction group was slightly higher than that of the non-gastrointestinal dysfunction group without statistically significant difference [ 43.75% ( 14/32 ) vs. 14.29% ( 1/7 ), P = 0.216 ]. It was shown by Pearson analysis that gastrointestinal dysfunction score was positively correlated with APACHEII score ( r = 0.727, P = 0.000 ), and the duration of gastrointestinal dysfunction was positively correlated with the length of ICU stay ( r = 0.797, P = 0.000 ) and the duration of mechanical ventilation ( r = 0.634, P = 0.000 ). CONCLUSIONS The results suggest that gastrointestinal function in patients with HS reflects the severity and prognosis of the ailment.