Acute kidney injury

A total of 597 of 3315 patients (18.0%) in the HES group and 566 of 3336 (17.0%) in the saline group died (relative risk in the HES group, 1.06; 95% confidence interval [CI], 0.96 to 1.18; P = 0.26). There was no significant difference in mortality in six predefined subgroups. Renal-replacement therapy was used in 235 of 3352 patients (7.0%) in the HES group and 196 of 3375 (5.8%) in the saline group (relative risk, 1.21; 95% CI, 1.00 to 1.45; P = 0.04). In the HES and saline groups, renal injury occurred in 34.6% and 38.0% of patients, respectively (P = 0.005), and renal failure occurred in 10.4% and 9.2% of patients, respectively (P = 0.12). HES was associated with significantly more adverse events (5.3% vs. 2.8%, P<0.001). Conclusions In patients in the ICU, there was no significant difference in 90-day mortality between patients resuscitated with 6% HES (130/0.4) or saline. However, more patients who received resuscitation with HES were treated with renal-replacement therapy. (Funded by the National Health and Medical Research Council of Australia and others; CHEST ClinicalTrials.gov number, NCT00935168.)

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Hydroxyethyl starch or saline for fluid resuscitation in intensive care

https://www.faa.gov/about/office_org/headquarters_offices/avs/offices/aam/ame/guide/media/STOP%20BANG%20Questionnaire.pdf

STOP-Bang Questionnaire: A Practical Approach to Screen for Obstructive Sleep Apnea.

Cardiolipin (CL) is a structurally unique dimeric phospholipid localized in the inner mitochondrial membrane where it is required for optimal mitochondrial function. In addition to its role in maintaining membrane potential and architecture, CL is known to provide essential structural and functional support to several proteins involved in mitochondrial bioenergetics. A loss of CL content, alterations in its acyl chain composition, and/or CL peroxidation have been associated with mitochondrial dysfunction in multiple tissues in a variety of pathological conditions, including ischemia, hypothyroidism, aging, and heart failure. Recently, aberrations in CL metabolism have been implicated as a primary causative factor in the cardioskeletal myopathy known as Barth syndrome, underscoring an important role of CL in human health and disease. The purpose of this review is to provide an overview of evidence that has linked changes in the CL profile to mitochondrial dysfunction in various pathological conditions. In addition, a brief overview of CL function and biosynthesis, and a discussion of methods used to examine CL in biological tissues are provided.

Role of cardiolipin alterations in mitochondrial dysfunction and disease

Enhanced Recovery After Surgery (ERAS) evidence-based protocols for perioperative care can lead to improvements in clinical outcomes and cost savings. This article aims to present consensus recommendations for the optimal perioperative management of patients undergoing cardiac surgery. A review of meta-analyses, randomized clinical trials, large nonrandomized studies, and reviews was conducted for each protocol element. The quality of the evidence was graded and used to form consensus recommendations for each topic. Development of these recommendations was endorsed by the Enhanced Recovery After Surgery Society.

/pdf/guidelines-for-perioperative-care-in-cardiac-surgery-1oaxfjbgom.pdf

Guidelines for Perioperative Care in Cardiac Surgery: Enhanced Recovery After Surgery Society Recommendations.

Background
Hydroxyethyl starches (HES) are synthetic colloids commonly used for fluid resuscitation to replace intravascular volume, yet they have been increasingly associated with adverse effects on kidney function. This is an update of a Cochrane review first published in 2010.

Objectives
To examine the effects of HES on kidney function compared to other fluid resuscitation therapies in different patient populations.

Search methods
We searched the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library), MEDLINE, EMBASE, MetaRegister and reference lists of articles. The most recent search was completed on November 19, 2012.

Selection criteria
Randomised controlled trials (RCTs) and quasi-RCTs in which HES was compared to an alternate fluid therapy for the prevention or treatment of effective intravascular volume depletion. Primary outcomes were renal replacement therapy (RRT), author-defined kidney failure and acute kidney injury (AKI) as defined by the RIFLE criteria.

Data collection and analysis
Screening, selection, data extraction and quality assessments for each retrieved article were carried out by two authors using standardised forms. All outcomes were analysed using relative risk (RR) and 95% confidence intervals (95% CI). Authors were contacted when published data were incomplete. Preplanned sensitivity and subgroup analyses were performed after data were analysed with a random-effects model.

Main results
This review included 42 studies (11,399 patients) including 19 studies from the original review (2010), as well as 23 new studies. Fifteen studies were excluded from the original review (nine retracted from publication due to concerns about integrity of data and six lacking individual patient creatinine data for the calculation of RIFLE criteria). Overall, there was a significant increase in the need for RRT in the HES treated individuals compared to individuals treated with other fluid therapies (RR 1.31, 95% CI 1.16 to 1.49; 19 studies, 9857 patients) and the number with author-defined kidney failure (RR 1.59, 95% CI 1.26 to 2.00; 15 studies, 1361 patients). The RR of AKI based on RIFLE-F (failure) criteria also showed an increased risk of AKI in individuals treated with HES products (RR 1.14, 95% CI 1.01 to 1.30; 15 studies, 8402 participants). The risk of meeting urine output and creatinine based RIFLE-R (risk) criteria for AKI was in contrast in favour of HES therapies (RR 0.95, 95% CI 0.91 to 0.99; 20 studies, 8769 patients). However, when RIFLE-R urine output based outcomes were excluded as per study protocol, the direction of AKI risk again favoured the other fluid type, with a non-significant RR of AKI in HES treated patients (RR 1.05, 95% CI 0.97 to 1.14; 8445 patients). A more robust effect was seen for the RIFLE-I (injury) outcome, with a RR of AKI of 1.22 (95% CI 1.08 to 1.37; 8338 patients). No differences between subgroups for the RRT and RIFLE-F based outcomes were seen between sepsis versus non-sepsis patients, high molecular weight (MW) and degree of substitution (DS) versus low MW and DS (≥ 200 kDa and > 0.4 DS versus 130 kDa and 0.4 DS) HES solutions, or high versus low dose treatments (i.e. ≥ 2 L versus < 2 L). There were differences identified between sepsis versus non-sepsis subgroups for the RIFLE-R and RIFLE-I based outcomes only, which may reflect the differing renal response to fluid resuscitation in pre-renal versus sepsis-associated AKI. Overall, methodological quality of the studies was good.

Authors' conclusions
The current evidence suggests that all HES products increase the risk in AKI and RRT in all patient populations and a safe volume of any HES solution has yet to be determined. In most clinical situations it is likely that these risks outweigh any benefits, and alternate volume replacement therapies should be used in place of HES products.

Hydroxyethyl starch (HES) versus other fluid therapies: effects on kidney function

BACKGROUND Obstructive sleep apnea (OSA) is associated with increased risk of postoperative complications. The authors investigated whether preoperative diagnosis and prescription of continuous positive airway pressure therapy reduces these risks. METHODS Matched cohort analysis of polysomnography data and Manitoban health administrative data (1987 to 2008). Postoperative outcomes in adult OSA patients up to 5 yr before (undiagnosed OSA, n = 1,571), and any time after (diagnosed OSA, n = 2,640) polysomnography and prescription of continuous positive airway pressure therapy for a new diagnosis of OSA, were compared with controls at low risk of having sleep apnea (n = 16,277). Controls were matched by exact procedure, indication, and approximate date of surgery. Procedures used to treat sleep apnea were excluded. Follow-up was at least 7 postoperative days. Results were reported as odds ratio (95% CI) for OSA or subgroup versus controls. RESULTS In multivariate analyses, the risk of respiratory complications (2.08 [1.35 to 3.19], P < 0.001) was similarly increased for both undiagnosed and diagnosed OSA. The risk of cardiovascular complications, primarily cardiac arrest and shock, was significantly different (P = 0.009) between undiagnosed OSA (2.20 [1.16 to 4.17], P = 0.02) and diagnosed OSA patients (0.75 [0.43 to 1.28], P = 0.29). For both outcomes, OSA severity, type of surgery, age, and other comorbidities were also important risk modifiers. CONCLUSIONS Diagnosis of OSA and prescription of continuous positive airway pressure therapy were associated with a reduction in postoperative cardiovascular complications. Despite limitations in the data, these results could be used to justify and inform large efficacy trials of perioperative continuous positive airway pressure therapy in OSA patients.

/pdf/a-matched-cohort-study-of-postoperative-outcomes-in-3lzfcu6w4j.pdf

A matched cohort study of postoperative outcomes in obstructive sleep apnea: could preoperative diagnosis and treatment prevent complications?

Background
Monolysocardiolipin acyltransferase (MLCL AT) catalyzes the acylation of monolysocardiolipin to cardiolipin in mammalian tissues. We previously reported that cardiac cardiolipin levels, MLCL AT and cardiolipin synthase activities were all elevated in rats made hyperthyroid by thyroxine treatment. In this study, we examined if cardiac mitochondrial MLCL AT activity was dependent upon the biosynthesis and level of cardiolipin in the heart. Rat heart mitochondrial MLCL AT activity was determined under conditions in which the levels of cardiac cardiolipin and cardiolipin synthase activity were either reduced or unaltered using four different disease models in the rat. In addition, these parameters were examined in a murine model of cardiac cell differentiation.

/pdf/expression-of-monolysocardiolipin-acyltransferase-activity-3lo4y9ezfw.pdf

Expression of monolysocardiolipin acyltransferase activity is regulated in concert with the level of cardiolipin and cardiolipin biosynthesis in the mammalian heart

Treatment of rats with thyroxine has been shown to elevate the biosynthesis and content of cardiolipin in the heart [Cao, Cheng, Angel and Hatch (1995) Biochim. Biophys. Acta 1256, 241-244]. Treatment with thyroxine resulted in a 1.8-fold increase (P<0.025) in [1-(14)C]linoleate and a 1.7-fold increase (P<0.025) in [1-(14)C]oleate incorporated into cardiolipin in perfused hearts, compared with controls. The mechanism for the elevation in incorporation of unsaturated fatty acids into cardiolipin was a 1. 6-fold (P<0.025) increase in mitochondrial monolysocardiolipin acyltransferase activity. The results demonstrate that the acylation of cardiac monolysocardiolipin is regulated by thyroid hormone. Thus an elevation in cardiolipin biosynthesis is accompanied by an elevation in monolysocardiolipin acyltransferase activity to maintain the appropriate molecular species composition of cardiolipin in the cardiac mitochondrial membrane. We postulate that monolysocardiolipin acyltransferase might be a rate-limiting enzyme for the molecular remodelling of cardiolipin in the heart.

/pdf/thyroxine-regulation-of-monolysocardiolipin-acyltransferase-3yeyhmhnfh.pdf

Thyroxine regulation of monolysocardiolipin acyltransferase activity in rat heart.

Dexamethasone prolongs the duration of interscalene block, but the benefits of higher doses and perineural vs intravenous administration remain unclear. This factorial design, double-blinded trial randomized 280 adult patients undergoing ambulatory arthroscopic shoulder surgery at a single centre in a 1:1:1:1 ratio. Patients received ultrasound-guided interscalene block with 30 mL 0.5% bupivacaine and 4 mg or 8 mg dexamethasone by either the perineural or intravenous route. The primary outcome (block duration measured as the time of first pain at the surgical site) and secondary outcomes (adverse effects, postoperative neurologic symptoms) were assessed by telephone. In this superiority trial, the predetermined minimum clinically important difference for comparisons between doses and routes was 3.0 hr. The perineural route significantly prolonged the mean block duration by 2.0 hr (95% confidence interval [CI], 0.4 to 3.5 hr; P = 0.01), but 8 mg of dexamethasone did not significantly prolong the mean block duration compared with 4 mg (1.3 hr; 95% CI, −0.3 to 2.9 hr, P = 0.10), and there was no significant statistical interaction (P = 0.51). The mean (95% CI) block durations, in hours, were 24.0 (22.9 to 25.1), 24.8 (23.2 to 26.3), 25.4 (23.8 to 27.0), and 27.2 (25.2 to 29.3) for intravenous doses of 4 and 8 mg and perineural doses of 4 and 8 mg, respectively. There were no marked differences in side effects between groups. At 14 postoperative days, 57 (20.4%) patients reported neurologic symptoms, including dyspnea and hoarseness. At six months postoperatively, only six (2.1%) patients had residual symptoms, with four (1.4%) patients’ symptoms unlikely related to interscalene block. Compared with the intravenous route, perineural dexamethasone prolongs the mean interscalene block duration by a small amount that may or may not be clinically significant, regardless of dose. However, the difference in mean block durations between 8 mg and 4 mg of dexamethasone is highly unlikely to be clinically important, regardless of the administration route. www.clinicaltrials.gov
 (NCT02426736). Registered 14 April 2015.

/pdf/effect-of-dexamethasone-dose-and-route-on-the-duration-of-4hkaig5585.pdf

Effect of dexamethasone dose and route on the duration of interscalene brachial plexus block for outpatient arthroscopic shoulder surgery: a randomized controlled trial.

Thomas C. Mutter

Papers

Hydroxyethyl starch (HES) versus other fluid therapies: effects on kidney function

A matched cohort study of postoperative outcomes in obstructive sleep apnea: could preoperative diagnosis and treatment prevent complications?

Expression of monolysocardiolipin acyltransferase activity is regulated in concert with the level of cardiolipin and cardiolipin biosynthesis in the mammalian heart

Thyroxine regulation of monolysocardiolipin acyltransferase activity in rat heart.

Effect of dexamethasone dose and route on the duration of interscalene brachial plexus block for outpatient arthroscopic shoulder surgery: a randomized controlled trial.