Journal of Pediatric Critical Care

P - ISSN : 2349-6592    |    E - ISSN : 2455-7099

Best Evidence Journal Scan
Year : 2016 | Volume : 3 | Issue : 4 | Page : 118-126

Journal Scan

Pragathesh Palaniappan*, Ebor Jacob James**

*Assistant Professor ,
** Professor Paediatric Intensive Care Unit
Christian Medical College, Vellore

Correspondence Address:

Ebor Jacob James
Professor Paediatric Intensive Care Unit,Christian Medical College, Vellore
Received: 01-Nov-16/Accepted: 15-Nov-16/Published online: 22-Nov-16

Source of Funding:None Conflict of Interest:None


Articles Reviewed
1. Urine KIM-1 as a Potential Biomarker of Acute Renal Injury After Circulatory Collapse in Children
Assadi F1, Sharbaf FG.. Pediatr Emerg Care. 2016 Oct 6.
This study was aimed to compare the diagnostic performance of 3 promising urinary biomarkers{urinary interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) }for the early detection of AKI in children with circulatory collapse.
This prospective cross-sectional study was performed in Dr. Sheikh Hospital of Mashhad University of Medical Sciences,between January and December 2015. Children with peripheral circulatory collapse who were admitted to the pediatric intensive care unit (PICU) were enrolled. Patients with known history of congenital or acquired kidney disease or urinary tract infections were excluded. Also excluded were patients with prior history of exposure to radiocontrast agents or treatment with nephrotoxic drugs such as anti-inflammatory nonsteroidal drugs.
Serum creatinine(, estimated creatinine clearance(eCrCL), urine IL-18, KIM-1, and NGAL values were measured within the first 8 hours of PICU admission, and the results were compared with those obtained 6 days later. Acute kidney injury was defined as a decreasein eCrCL of greater than 25% within the first 48 hours of enrollment. Areas under the curve (AUC) for receiver operating characteristic curve were calculated for the early detection of AKI. A total of 86 patients, between the ages of 7 months and 14 years, were enrolled. Mean SCr concentration did not differ significantly during the first 6 days of hospital admission. In contrast, mean urine concentrations of IL-18, KIM-1, and NGAL rose significantly fromday of admission to the sixth day of hospital stay (P < 0.001). Urinary KIM-1 emerged as having the strongest performance for the early detection of AKI, followed by NGAL, IL-18, and eCrCL. Urinary KIM-1 displayed the highest AUC of 0.81 (95% confidence interval [CI], 0.76-0.93; P < 0.001) for the early detection of AKI after circulatory collapse, followed by NGAL (0.77% CI,0.70–0.84) and IL-18 (0.69% CI, 0.48–0.64)

KIM-1demonstrated the best performance in predicting AKI in children with circulatory collapse before a change in SCr or eCrCL becomes apparent. Moreover panel of 3 biomarkers, rather than a single biomarker, may provide better performance to predict the early development of AKI.

Comments: The criteria for the diagnosis of AKI in children, are not reliable because of the lag time between the initiating injury and identification of renal dysfunction (Serum creatinine, eCrCL) which may delay effective therapies that are limited to the early stage. These three biomarkers enable us to identify the renal dysfunction at the early stage so that appropriate therapy can be initiated at the earliest.

2. Use of Transcranial Doppler for Management of Central Nervous System Infections in Critically Ill Children
Ducharme-Crevier L, Mills MG, Mehta PM, Smith CM, Wainwright MS. Pediatr Neurol. 2016 Sep 4 ; 1-7

The primary objective of this study was to characterize changes in cerebral blood flow(CBF) measured using transcranial Doppler in children with central nervous system infections. In adults with meningitis, variable patterns of cerebral blood flow (CBF) have been described, including an increase correlating to the type of bacterial pathogen, hyperemia in patients with reassuring clinical state, decrease caused by cerebral edema, and vasospasm. Transcranial Doppler (TCD) ultrasonography permits dynamic monitoring of blood flow velocities in major intracerebral arteries and is a surrogate for CBF.
This is a single-center, retrospective descriptive study of children admitted to the neonatal or pediatric intensive care unit with central nervous system infection and undergoing transcranial Doppler as part of routine care between March 2011 and July 2015.
A total of 20 children with central nervous system infection underwent 35 transcranial Dopplers. The mean age was 8.2 + 6.3 years, including 12 boys and eight girls. Most cases were caused by meningitis (n = 11, 55%), the remainder comprising encephalitis (15%), meningoencephalitis (20%), and abscess or empyema (10%). Bacterial (n =10, 50%) and viral (n =6) sources were common with only one (5%) fungal infection and three (15%) unknown but presumed viral etiology. The patients underwent transcranial Doppler 4 + 9 days after intensive care unit admission. Mean cerebral blood flow velocities were overall increased compared with reference values for age (healthy children and critically ill children) . Mean CBFV patterns was classified further into two categories: (1) the presence of hypoperfusion in at least one vessel (low CBFV or vasospasm) and (2) hyperemia or normal flow. In this study 60% had hyperemia and 6% had vasospasm. Hypoperfusion (cerebral blood flow velocity <1 S.D. of normal value) in at least one vessel was associated with morbidity (intubation, vasoactive medications, neurosurgery, cardiac arrest) (P =0.04) and mortality (P =0.03). There was a nonsignificant trend toward increased risk for seizures in patients with the presence of hypoperfusion in at least one vessel (P =0.1).Among nine patients with raised ICT, TCD showed hyperemia in six, hypoperfusion with increased PI in two, and normal velocities in one. There was no association between abnormal TCD pattern and clinical or radiological signs of increased ICP (P = 0.7).

Transcranial Doppler can be used in children with central nervous system infection as a tool to assess cerebral blood flow. In this retrospective study, cerebral hypoperfusion was associated with increased morbidity and mortality. If transcranial Doppler is to guide medical therapy and management of cerebral blood flow in children with central nervous system infections, these results will need to be validated in prospective studies with a more homogenous population of children with encephalitis or meningitis.

In meningitis, variable patterns of cerebral blood flow (CBF) have been described especially in adults. Incase of any CNS insult, cerebral blood flow is altered depending upon the severity of the ICP. Though the CBFV correlation with ICP is not statistically significant, hypoperfusion was associated with significant morbidity and mortality . The limitations of this study was that there is no definitive timing of TCD study i.e., the TCDs were performed at the discretion of the neurocritical care service request and may be subject to a selection bias. Moreover CBF is influenced by a number of physiological parameters, such as temperature, systemic blood pressure, PaCO2, PaO2, hemoglobin, and CBFV is also influenced by the diameter of the imaged vessels, which may have significant influence on the results.

3. Beta-Lactam Infusion in Severe Sepsis (BLISS):a prospective, two-centre, open-labelled randomised controlled trial of continuous versus intermittent beta-lactam infusion in critically ill patients with severe sepsis
Abdul-Aziz MH1,2, Sulaiman H3, Mat-Nor MB4, Rai V5, Wong KK et al. Intensive Care Med. 2016 Oct;42(10):1535-45

This study was aimed to determine whether continuous infusion (CI) of Beta-Lactamis is associated with better clinical and pharmacokinetic/pharmacodynamic(PK/PD) outcomes compared to intermittent bolus (IB) dosing in critically ill patients with severe sepsis.
This BLISS study was a prospective, two-centre, open labelled RCT of CI versus IB dosing of beta-lactam antibiotics in critically ill patients with severe sepsis from the two following Malaysian ICUs. ICU patients were eligible for inclusion if they met all of the following criteria: (1) adult (C18 years); (2) developed severe sepsis (defined as presumed or confirmed infection with new organ dysfunction) [24] in the previous 48 h; (3) indication for Cefepime, Meropenem or Piperacillin/Tazobactam with \24 h therapy at time of assessment; and (4) expected ICU stay greater than 48 h. Patients were excluded if they (1) were receiving renal replacement therapy (RRT); (2) had impaired hepatic function (defined as total bilirubin [100 lmol/mL); (3)were receiving palliative treatment; (4) had inadequate central venous catheter access; or (5) death was deemed imminent. Participants currently receiving, or about to receive,Cefepime, Meropenem or Piperacillin/Tazobactam were randomly allocated to either a CI (intervention arm) or IB (control arm) treatment arm. The primary outcome was clinical cure at 14 days after antibiotic cessation. Secondary outcomes were PK/PD target attainment, ICU-free days and ventilator-free days at day 28 postrandomisation, 14- and 30-day survival, and time to white cell count normalisation.
A total of 140 participants were enrolled with 70 participants each allocated to CI and IB dosing. CI participants had higher clinical cure rates (56 versus 34 %, p = 0.011) and higher median ventilator-free days (22 versus14 days, p\0.043) than IB participants. PK/PD target attainment rates were higher in the CI arm with unbound (free) plasma concentration at 100 % of the dosing interval (trough concentration) was above the causative pathogens MIC(100 % fT> MIC) than the IB arm on day 1 (97 versus 70 %, p\0.001) and day 3(97 versus 68 %, p\0.001) postrandomisation. There was no difference in 14-day or 30-day survival between the treatment arms.

Beta-lactam antibiotics display time-dependent activity where bacterial killing and treatment efficacy correlate with the duration of time (T) that free (unbound) plasma drug concentrations remain above the minimum inhibitory concentration (MIC) of the offending pathogen (fT>MIC).So, maximal betalactam effects are considered more likely with continuous infusion (CI) rather than traditional intermittent bolus (IB) dosing. IB dosing may produce beta-lactam concentrations below the MIC for much of the dosing interval particularly in the ICU where pathogens with higher MIC values are relatively common.

In critically ill patients with severe sepsis not receiving RRT, CI demonstrated higher clinical cure rates and had better PK/PD target attainment compared to IB dosing of beta-lactam antibiotics. Continuous beta-lactam infusion may be mostly advantageous for critically ill patients with high levels of illness severity and not receiving RRT.

4. Conservative fluid management or deresuscitation for patients with sepsis or acute respiratory distress syndrome following the resuscitation phase of critical illness: a systematic review and meta analysis
Silversides JA, Major E, Ferguson AJ, Mann EE, McAuley DF, Marshall JC, Blackwood B, Fan E. Intensive Care Med. 2016 Oct 12

This study was aimed to evaluate the efficacy and safety of conservative or deresuscitative fluid strategies in adults and children with acute respiratory distress syndrome (ARDS), sepsis or systemic inflammatory response syndrome (SIRS) in the post-resuscitation phase of critical illness. Medline, EMBASE and the Cochrane central register of controlled trials have been searched from 1980 to June 2016, and relevant conference proceedings from 2009 to the present were manually reviewed. The study included randomised and quasi-randomised clinical trials of adult or paediatric patients with ARDS, SIRS or sepsis in which two or more fluid strategies were compared and in which fluid balance differed between groups; and observational studies in which the relationship between fluid balance and clinical outcomes in ARDS, SIRS or sepsis was the major focus of the study. The studies that focused only on the resuscitation phase of critical illness, and studies in which fluids were only one element of a complex haemodynamic strategy are excluded. The studies which are case series, case reports, observational studies with fewer than 50 participants, studies published prior to 1980, studies involving predominantly neonates, post-cardiac surgery patients, or patients with heart failure, and studies subject to postpublication retraction or investigation were excluded. Two reviewers independently assessed search results for inclusion and undertook data extraction and quality appraisal. The primary outcome was all-cause mortality at the latest time point available up to 90 days. Key secondary outcomes included ventilator-free days (VFDs), length of intensive care unit (ICU) stay, incidence of AKI, renal replacement therapy (RRT) use, and cognitive impairment. Forty-nine studies met the inclusion criteria. Marked clinical heterogeneity was evident.
In a meta-analysis of 11 randomised trials (2051 patients) using a random-effects model, it was found no significant difference in mortality with conservative or deresuscitative strategies compared with a liberal strategy or usual care [pooled risk ratio (RR)0.92, 95 % confidence interval (CI) 0.82–1.02, I2 = 0 %]. A conservative or deresuscitative strategy resulted in increased ventilator-free days (mean difference 1.82 days, 95 % CI 0.53–3.10, I2= 9 %) and reduced length of ICU stay (mean difference−1.88 days, 95 % CI −0.12 to −3.64, I2 = 75 %) compared with a liberal strategy or standard care.

Conclusion: In adults and children with ARDS, sepsis or SIRS, a conservative or deresuscitative fluid strategy results in an increased number of ventilator-free days and a decreased length of ICU stay compared with a liberal strategy or standard care. The effect on mortality remains uncertain. Large randomised trials are needed to determine optimal fluid strategies in critical illness.

Optimising fluid status is a fundamental concern of critical care practice because it increases cardiac output and global oxygen delivery. In the face of increased capillary permeability, sodium and water retention, and acute kidney injury (AKI), all of which are common in critical illness, the accumulation of large volumes of fluid in the interstitium is a frequent occurrence and may impair oxygen delivery at the cellular level. Clinically this fluid overload is apparent as peripheral and pulmonary oedema, although other organs may be affected. This metaanalysis shows that conservative or deresuscitative fluid strategies have significant reduction in the ventilator free days, but there is no significant effect on the mortality.

5. Pediatric extubation readiness tests should not use pressure support
Khemani RG, Hotz J, Morzov R, Flink RC, Kamerkar A, LaFortune M, Rafferty GF, Ross PA , Newth CJ .
Intensive Care Med. 2016 Aug;42(8):1214-22

This study was aimed to compare the effect of pressure support CPAP on breathing effort prior to Extubation with the post-extubation breathing effort. The study hypothesis was that the effort of breathing on CPAP of 5 cmH2O was not higher than post-extubation and that using pressure support prior to extubation would significantly underestimate post-extubation effort.
This is a prospective trial which included all intubated children in the pediatric and cardiothoracic intensive care units at the Children’s Hospital Los Angeles from July 2012 to April 2015. Inclusion criteria were children greater than 37 weeks gestational age to 18 years, intubated for at least 12 h with extubation from 7 am to5 pm Monday–Friday. Exclusion criteria were contraindication for placement of esophageal catheter or respiratory inductance plethysmography bands. An esophageal balloon catheter and respiratory inductance plethysmography bands calibrated under tidal breathing on CPAP of 5 cmH2O was placed in all the participants prior to extubation. A self-calibrating pneumotachometer was used prior to extubation to measure peak inspiratory flow during tidal breathing. When the clinical team determined that the patient was ready for extubation, data were recorded under four conditions in the following order: pressure support 10/PEEP 5 cmH2O, CPAP 5 cmH2O (CPAP), and spontaneous breathing, 5 min and 60 min after extubation. Pressure support and CPAP measurements were within 20 min of extubation. Median pressure rate product {= peak-to-trough change in esophageal pressure (cmH2O) × respiratory rate (breaths per minute)}over the entire 5 min was calculated in all four conditions.
For the entire cohort (n = 409), Pressure rate product on pressure support [100 (IQR 60, 175)] was lower than CPAP [200 (120, 300)], which was lower than 5 min [300 (150, 500)] and 60 min [255 (175, 400)] post-extubation (all p < 0.01). Excluding 107 patients with post-extubation UAO (where pressure rate product after extubation is expected to be higher), pressure support still underestimated post-extubation effort by 126–147 %, and CPAP underestimated post-extubation effort by 17–25 %. For all endotracheal tube subgroups, ≤3.5 mmID (n = 152), 4–4.5 mmID (n = 102),and ≥5.0 mmID (n = 48), pressure rate product on pressure support was lower than CPAP and post-extubation (all p < 0.0001), while CPAP pressure rate product was not different from post-extubation (all p < 0.05). These findings were similar for patients extubated to noninvasive respiratory support, where pressure rate product on pressure support before extubation was significantly lower than pressure rate product post-extubation on noninvasive respiratory support (p < 0.0001, n = 81).

Pressure support should not be added to CPAP to overcome “imposed work of breathing” from the endotracheal tube during spontaneous breathing trials or extubation readiness tests in children. Regardless of the size of the endotracheal tube, the use of pressure support significantly underestimates post-extubation effort of breathing (125–150 % underestimation).

It’s a common practice to add pressure support during extubation readiness tests to overcome perceived imposed resistance of the endotracheal tube. The breathing effort of the patient is low on CPAP/PS compared to CPAP.Similarly the breathing effort is low on CPAP compared to post. The application of pressure support to CPAP underestimates the patient’s breathing effort. In other words, if patient effort of breathing is high on CPAP 5 cmH2O prior to extubation, they are unlikely to do well after extubation, even with noninvasive respiratory support. While inspiratory resistance increases as endotracheal tube size decreases, prior to extubation children are breathing with flow rates where predicted inspiratory resistance is actually below extubated values. Therefore, this study showed no evidence to support adding pressure support to “reduce imposed work of breathing” during extubation readiness tests in children, regardless of the endotracheal tube size.

6. Effect of Chlorhexidine Bathing Every Other Day on Prevention of Hospital-Acquired Infections in the Surgical ICU: A Single-Center, Randomized Controlled Trial (CHG-BATH Trial)
Swan JT, Ashton CM, Bui LN, Pham VP et al Crit Care Med. 2016 Oct;44(10):1822-32

To test the hypothesis that compared with daily soap and water bathing, 2% chlorhexidine gluconate bathing every other day for up to 28 days decreases the risk of hospital-acquired catheter-associated urinary tract infection, ventilator-associated pneumonia, incisional surgical site infection, and primary bloodstream infection in surgical ICU patients.
The CHG-BATH trial was a pragmatic, single-center, open label, randomized trial conducted in a 24-bed SICU at Houston Methodist Hospital, a quaternary academic medical center. Patients and clinicians were aware of treatment-group assignment; investigators who determined outcomes were blinded. The SICU provides care for general surgical patients and a large liver failure population before and after liver transplant. The hypothesis that compared with soap and water daily bathing, 2% chlorhexidine gluconate bathing on ICU admission and every 48 hours during SICU care for up to 28 days will decrease the risk of acquiring four HAIs (CAUTI, VAP, incisional SSI, and primary BSI) in SICU patients was tested in this study. Patients and bedside clinicians were aware of treatment group assignment, but investigators who determined efficacy and safety outcomes were blinded. Patients were randomized within 48 hours of SICU admission. Patients were bathed per protocol during the bathing period, which started at randomization and ended at SICU discharge, day 28, or death, whichever occurred first. Patient level information was collected daily during the observation period, which includes the bathing period plus up to 48 hours of additional follow-up. All patients admitted to the SICU from July 2012 to May 2013 were screened for eligibility. Adults (≥ 18 years old) with an anticipated SICU stay for 48 hours or more were eligible. Patients with a Braden Scale for Predicting Pressure Sore Risk(26) score less than 9 (highest risk), pregnancy, skin irritation that precluded chlorhexidine bathing, chlorhexidine allergy, or an SICU stay of more than 48 hours prior to screening were excluded Beginning on the day of randomization, patients received daily wash basin-based baths per protocol until SICU discharge, day 28, or death, whichever occurred first. In the control arm, patients were bathed daily with soap and water. In the treatment arm, patients were bathed with chlorhexidine every other day (starting study day 1) alternating with soap and water every other day. Prior to trial initiation, all SICU nurses and patient care assistants were educated on the protocol. A charge nurse or nursing manager audited bathing compliance daily. The protocol mandated that washbasins be discarded after each study bath (in both arms) to prevent colonization
Soap and water baths were predominately provided with non medicated bath washcloths which are compatible with chlorhexidine . This procedure was also used to provide soap and water baths every other day in the chlorhexidine arm. These soap and water baths were the standard of care in this SICU prior to trial initiation. Patients in both study arms also received ad hoc soap and water baths to cleanse bodily fluids such as urine, feces, and blood. Ad hoc baths were restricted to soiled skin areas only. The frequency of use of ad hoc baths was not recorded. Chlorhexidine bathing consisted of the following steps. First, Bedside-Care bath washcloths were used to remove soiled material from skin and to cleanse face, open wounds, and perianal areas. The washbasin was emptied and filled with a 2% chlorhexidine solution created by mixing 8 oz of warm tap water with 8 oz (two 4-oz bottles) of Bactoshield chlorhexidine 4% Surgical Scrub Disposable or terrycloth washcloths submerged into the 2% chlorhexidine solution were used to bathe the entire body except for the face, perianal mucous membranes, and open wounds. The chlorhexidine was allowed to air-dry without rinsing to create a chlorhexidine barrier.

The primary endpoint was acquisition of an incident CAUTI, VAP, incisional SSI, or primary BSI . Infections detected more than 48 hours after randomization and prior to the end of follow-up were classified as incident infections. Infections detected prior to or within 48 hours of randomization were classified as prevalent infections. Surveillance for infection (cultures and imaging) was ordered per routine care and was not standardized per protocol. The 2008 Centers for Disease Control and Prevention (CDC) surveillance definitions were used, with a modification to the definition of abnormal temperature to include less than 36°C and greater than 38°C (28, 29). For CAUTI, March 2010 CDC update and 2013 CDC requirement of symptoms within 1 day of urine culture was adopted. Pneumonias detected after 48 hours of mechanical ventilation were classified as VAP.
If a patient developed two infections of the same type (e.g., two BSIs), the second infection was not included. If a patient developed two incident infections of different types (e.g., VAP and CAUTI), both infections were included. Secondary Endpoints were rates of CAUTI, VAP, incisional SSI, and primary BSI per 1,000 days at risk, in-hospital mortality, and length of time from randomization until first SICU discharge and hospital discharge. Safety endpoints were incident adverse skin occurrences. The proportional-hazards assumption was met for this analysis (p = 0.061).
The primary endpoint was a composite outcome of catheter-associated urinary tract infection, ventilator-associated pneumonia, incisional surgical site infection, and primary blood stream infection. Of 350 patients randomized, 24 were excluded due to prior enrollment in this trial and one withdrew consent. Therefore, 325 were analyzed (164 soap and water versus 161 chlorhexidine). Fifty-three incident HAIs (35 with soap and water versus 18 with chlorhexidine) were detected. Compared with soap and water bathing alone, intermittent chlorhexidine bathing decreased the risk of acquiring HAIs (Hazard ratio R = 0.555; 95% CI, 0.309–0.997; p = 0.049) by 44% in an unadjusted primary analysis. For patients bathed with soap and water versus chlorhexidine, counts of incident hospital-acquired infections were 14 versus 7 for catheter-associated urinary tract infection, 13 versus 8 for ventilator-associated pneumonia, 6 versus 3 for incisional surgical site infections, and 2 versus 0 for primary bloodstream infection; the effect was consistent across all infections. The absolute risk reduction for acquiring a hospital-acquired infection was 9.0% (95% CI, 1.5-16.4%; p = 0.019). Incidences of adverse skin occurrences were similar (18.9% soap and water vs 18.6% chlorhexidine; p = 0.95).

Compared with soap and water, chlorhexidine bathing every other day decreased the risk of acquiring infections by 44.5% in surgical ICU patients. Full-body bathing with chlorhexidine every other day reduced the risk of acquiring the composite outcome of four HAIs (CAUTI, VAP, incisional SSI, and primary BSI) in SICU patients by 44.5%. Intermittent chlorhexidine bathing did not increase the risk of adverse skin occurrences. This inexpensive, safe, and easy to implement intervention prevents HAIs in SICU patients who are expected to require at least 48 hours of ICU care. The association between chlorhexidine bathing and prevention of multiple types of infection observed in this trial should be confirmed in another clinical trial of patients who have a high risk of acquiring HAIs.

There is growing evidence to support that bathing ICU patients with chlorhexidine gluconate, a topical antiseptic that rapidly kills common HAI-causing pathogens, prevents colonization from HAI-causing pathogens, prevents bloodstream infections (BSIs), and may prevent other types of HAIs . In 2013, three multicenter trials that randomized either ICUs or hospitals found that compared with daily bathing with soap and water, daily bathing with chlorhexidine reduced BSIs by 28–44%. However, these trials did not examine a treatment effect of chlorhexidine for prevention of catheter-associated urinary tract infection (CAUTI), ventilator-associated pneumonia (VAP), or incisional surgical site infection (SSI) and did not evaluate the treatment effect of chlorhexidine bathing at the individual patient level.
CHG-BATH trial is the first trial evaluating chlorhexidine bathing in ICU patients that randomized on the patient level and enrolled patients who were predicted to require at least 48 hours of ICU care, which selected patients at highest risk for acquiring HAIs. In this trial, full-body bathing with chlorhexidine every other day reduced the risk of acquiring the composite outcome of four HAIs (CAUTI, VAP, incisional SSI, and primary BSI) in SICU patients by 44%. The absolute risk reduction for acquiring an HAI was 9%, equating to bathing 11 patients to prevent one HAI. Chlorhexidine bathing did not increase the risk of adverse skin occurrences or pressure ulcers.
Previous chlorhexidine bathing trials used cluster randomization and intervened at the group-level, and may be at risk for ecological inference fallacy if individual exposure to chlorhexidine was not accounted for in the analysis. By randomizing on the patient level, the present trial provides evidence that prescribing chlorhexidine bathing for individual patients prevents HAIs. It is not clear whether the treatment effect observed in this trial was through decreasing the risk of infection from the patient’s own micro biota, decreasing the risk of patient-to patient transmission, or both.
This study was not powered to detect differences in the incidence of individual infection types, hospital length of stay, or in-hospital mortality. The protocol mandated that washbasins be discarded after each bath, but compliance with this mandate was not tracked. This trial used a pragmatic design that ensured maximum generalizability by using minimal inclusion and exclusion criteria, causing minimal interference with normal processes of care and emphasizing the use of data routinely collected within the hospital’s electronic medical record. Non investigator bedside nurses and patient care assistants provided chlorhexidine bathing, investigators did not monitor the quality of baths provided, and concentrations of chlorhexidine in the bathing solution were not measured; while these attributes may decrease the internal validity ,they increase the external validity of this trial

7. Nitric oxide administration during paediatric cardiopulmonary bypass: a randomised controlled trial.
James C, Millar J, Horton S, Brizard C, Molesworth C, Butt W. Intensive Care Med. 2016 Nov;42(11):1744-1752.
Summary :

Cardiopulmonary bypass induces an ischaemia–reperfusion injury and systemic inflammatory response, which contributes to low cardiac output syndrome following cardiac surgery. There is a predictable drop in cardiac output following cardiac surgery and cardiopulmonary bypass (CPB) in children . The clinical picture associated with this fall in cardiac output, low cardiac output syndrome (LCOS), delays recovery and is associated with significant morbidity and mortality. Attenuation of this phenomenon could have significant implications for clinical outcome. Exogenous nitric oxide during cardiopulmonary bypass has shown potential to ameliorate such injury. This large randomised controlled trial was done to investigate the clinical effects of administering nitric oxide to the cardiopulmonary bypass circuit in children.
After written informed consent, children were randomised to receive 20 ppm nitric oxide to the gas inflow of the cardiopulmonary bypass oxygenator, or standard conduct of bypass. The per fusionists alone was unblinded and was responsible for NO delivery. Exclusion criteria were administration of inhaled NO immediately prior to surgery or emergency surgery. Sample size was determined with 80 % power to detect a 40 % reduction in LCOS with a significance level of 0.05. Assumptions for the control group and treatment effect were based on data reported by Checchia and colleagues. Patients were randomised into two groups: NO group (NO added to the oxygenator gas inflow at 20 ppm throughout CPB) and control group (standard conduct of CPB). The primary outcome was LCOS, defined as any of the following at any time during the first 48 h:
1. Lactate >4 mmol/l and ScvO2 <60 % (or SaO2–ScvO2 difference >35 % in single ventricle)
2. VIS ≥ 10
3. ECMO.
Secondary outcome measures were use of iNO, use of peritoneal dialysis, delayed sternal closure, blood loss, blood product transfusion, duration of mechanical ventilation, length of ICU and hospital stay.
During the study period 490 congenital cardiac operations were performed using CPB. A total of 198 children were enrolled: 101 in the NO group and 97 in the control group. Those children who received nitric oxide developed low cardiac output syndrome less frequently (15 vs. 31 %, p = 0.007) than the 97 children who did not receive nitric oxide. This effect was most marked in children aged less than 6 weeks of age (20 vs. 52 %, p = 0.012) and in those aged 6 weeks to 2 years (6 vs. 24 %, p = 0.026), who also had significantly reduced ICU length of stay (43 vs. 84 h, p = 0.031). Low cardiac output syndrome was less frequent following more complex surgeries if nitric oxide was administered (17 vs. 48 %, p = 0.018). ECMO was used less often in the nitric oxide group (1 vs. 8 %, p = 0.014).
There were no differences in duration of ventilation, ICU stay or hospital stay between groups . NO group patients received iNO less often than the control group (3 vs. 12 %, p = 0.015). iNO was initiated in the operating theatre or within 4 h of admission to ICU to treat pulmonary hypertension or poor oxygenation in all but one case (control group), where NO was initiated 1 month after ICU admission. There was no difference between groups in the amount of bleeding in the first 24 h. Seventeen patients had delayed sternal closure (eight NO, nine control). Sixteen were admitted with an open sternum; the remaining patient had emergency chest opening after 24 h because of refractory LCOS./
No cardiac arrests occurred during the 48-h post-operative period. There were three later cardiac arrests, each with successful return of circulation. No deaths occurred during the 48-h post-operative period. Four patients (control group) died before ICU discharge, 2 weeks to 2 months after surgery (bidirectional cavopulmonary shunt, hypoplastic left heart syndrome; rhabdomyoma removal with Norwood procedure; hypoplastic aortic arch and ventricular septal defect (VSD) repair; tetralogy of Fallot repair with hypoplastic pulmonary arteries).

Administration of nitric oxide to the CPB oxygenator during paediatric cardiac surgery reduced the incidence of post-operative low cardiac output syndrome. This effect was age-dependent, with the greatest effect observed in younger children. This safe and relatively simple intervention has the potential to improve short-term outcomes for children undergoing cardiac surgery. Larger studies are needed to validate these findings.

This study showed that the administration of iNo to the CPB oxygenator in children undergoing cardiac surgery reduced the incidence of postoperative LCOS. This effect was most markedly seen in children less than 2 years undergoing complex surgery. There is ample evidence exists to show NO mediated protection from ischemia –reperfusion injury in the heart and other organs. This is the second such study of NO administration directly to the CPB oxygenator to children after the study by Checchia and colleagues. There are some limitations to this study Forty per cent of eligible patients were not included because of limited availability of a small research team. Those who were not included did not differ in age, weight or risk of surgery from the study cohort. For safety reasons the perfusionist was not blinded to group allocation. Although all other staff were blinded, conduct of CPB was identical in both groups and NO administration was not identified in the patient record, this is a potential source of bias. Control placebo gas has been used in trials investigating the effect of NO in the past. In this study use of control placebo gas was not done as it may complicate the conduct of CPB. Although the number of patients in the study is relatively large, this single-centre investigation is limited in its general applicability. Local practices regarding conduct of anaesthesia, CPB, surgery, ECMO deployment and post-operative care may all have influenced outcomes