Interventions for preventing upper gastrointestinal bleeding in people admitted to intensive care units

This systematic review by Toews and colleagues was published in the Cochrane Database in June 2018.cochrane-57-1

Background:  Upper gastrointestinal (GI) bleeding due to stress ulcers contributes to increased morbidity and mortality in people admitted to intensive care units (ICUs). Stress ulceration refers to GI mucosal injury related to the stress of being critically ill. ICU patients with major bleeding as a result of stress ulceration might have mortality rates approaching 48.5% to 65%. However, the incidence of stress-induced GI bleeding in ICUs has decreased, and not all critically ill patients need prophylaxis. Stress ulcer prophylaxis can result in adverse events such as ventilator-associated pneumonia; therefore, it is necessary to evaluate strategies that safely decrease the incidence of GI bleeding.

Objectives:  To assess the effect and risk-benefit profile of interventions for preventing upper GI bleeding in people admitted to ICUs.
Search Methods:  We searched the following databases up to 23 August 2017, using relevant search terms: MEDLINE; Embase; the Cochrane Central Register of Controlled Trials; Latin American Caribbean Health Sciences Literature; and the Cochrane Upper Gastrointestinal and Pancreatic Disease Group Specialised Register, as published in the Cochrane Library (2017, Issue 8). We searched the reference lists of all included studies and those from relevant systematic reviews and meta-analyses to identify additional studies. We also searched the World Health Organization International Clinical Trials Registry Platform search portal and contacted individual researchers working in this field, as well as organisations and pharmaceutical companies, to identify unpublished and ongoing studies.
Selection Criteria:  We included randomised controlled trials (RCTs) and quasi-RCTs with participants of any age and gender admitted to ICUs for longer than 48 hours. We excluded studies in which participants were admitted to ICUs primarily for the management of GI bleeding and studies that compared different doses, routes, and regimens of one drug in the same class because we were not interested in intraclass effects of drugs.

Data collection and analysis:  We used standard methodological procedures as recommended by Cochrane.
Main results:  We identified 2292 unique records.  We included 129 records reporting on 121 studies, including 12 ongoing studies and two studies awaiting classification.  We judged the overall risk of bias of two studies as low. Selection bias was the most relevant risk of bias domain across the included studies, with 78 studies not clearly reporting the method used for random sequence generation. Reporting bias was the domain with least risk of bias, with 12 studies not reporting all outcomes that researchers intended to investigate.  Any intervention versus placebo or no prophylaxisIn comparison with placebo, any intervention seems to have a beneficial effect on the occurrence of upper GI bleeding (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.39 to 0.57; moderate certainty of evidence). The use of any intervention reduced the risk of upper GI bleeding by 10% (95% CI -12.0% to -7%). The effect estimate of any intervention versus placebo or no prophylaxis with respect to the occurrence of nosocomial pneumonia, all-cause mortality in the ICU, duration of ICU stay, duration of intubation (all with low certainty of evidence), the number of participants requiring blood transfusions (moderate certainty of evidence), and the units of blood transfused was consistent with benefits and harms. None of the included studies explicitly reported on serious adverse events.  Individual interventions versus placebo or no prophylaxisIn comparison with placebo or no prophylaxis, antacids, H2 receptor antagonists, and sucralfate were effective in preventing upper GI bleeding in ICU patients. Researchers found that with H2 receptor antagonists compared with placebo or no prophylaxis, 11% less developed upper GI bleeding (95% CI -0.16 to -0.06; RR 0.50, 95% CI 0.36 to 0.70; 24 studies; 2149 participants; moderate certainty of evidence). Of ICU patients taking antacids versus placebo or no prophylaxis, 9% less developed upper GI bleeding (95% CI -0.17 to -0.00; RR 0.49, 95% CI 0.25 to 0.99; eight studies; 774 participants; low certainty of evidence). Among ICU patients taking sucralfate versus placebo or no prophylaxis, 5% less had upper GI bleeding (95% CI -0.10 to -0.01; RR 0.53, 95% CI 0.32 to 0.88; seven studies; 598 participants; moderate certainty of evidence). The remaining interventions including proton pump inhibitors did not show a significant effect in preventing upper GI bleeding in ICU patients when compared with placebo or no prophylaxis.  Regarding the occurrence of nosocomial pneumonia, the effects of H2 receptor antagonists (RR 1.12, 95% CI 0.85 to 1.48; eight studies; 945 participants; low certainty of evidence) and of sucralfate (RR 1.33, 95% CI 0.86 to 2.04; four studies; 450 participants; low certainty of evidence) were consistent with benefits and harms when compared with placebo or no prophylaxis. None of the studies comparing antacids versus placebo or no prophylaxis provided data regarding nosocomial pneumonia.H2 receptor antagonists versus proton pump inhibitorsH2 receptor antagonists and proton pump inhibitors are most commonly used in practice to prevent upper GI bleeding in ICU patients. Proton pump inhibitors significantly more often prevented upper GI bleeding in ICU patients compared with H2 receptor antagonists (RR 2.90, 95% CI 1.83 to 4.58; 18 studies; 1636 participants; low certainty of evidence). When taking H2 receptor antagonists, 4.8% more patients might experience upper GI bleeding (95% CI 2.1% to 9%). Nosocomial pneumonia occurred in similar proportions of participants taking H2 receptor antagonists and participants taking proton pump inhibitors (RR 1.02, 95% CI 0.77 to 1.35; 10 studies; 1256 participants; low certainty of evidence).

Authors’ Conclusions:  This review shows that antacids, sucralfate, and H2 receptor antagonists might be more effective in preventing upper GI bleeding in ICU patients compared with placebo or no prophylaxis. The effect estimates of any treatment versus no prophylaxis on nosocomial pneumonia were consistent with benefits and harms. Evidence of low certainty suggests that proton pump inhibitors might be more effective than H2 receptor antagonists. Therefore, patient-relevant benefits and especially harms of H2 receptor antagonists compared with proton pump inhibitors need to be assessed by larger, high-quality RCTs to confirm the results of previously conducted, smaller, and older studies.
The full text of this review is freely available from the Cochrane Database of Systematic Reviews via this link.


BIS monitoring versus clinical assessment for sedation in mechanically ventilated adults in the intensive care unit and its impact on clinical outcomes and resource utilization

cochrane-57-1This Cochrane Systematic Review by Shety and colleagues was published on 21 February 2018

BackgroundPatients admitted to intensive care and on mechanical ventilation, are administered sedative and analgesic drugs to improve both their comfort and interaction with the ventilator. Optimizing sedation practice may reduce mortality, improve patient comfort and reduce cost. Current practice is to use scales or scores to assess depth of sedation based on clinical criteria such as consciousness, understanding and response to commands. However these are perceived as subjective assessment tools. Bispectral index (BIS) monitors, which are based on the processing of electroencephalographic signals, may overcome the restraints of the sedation scales and provide a more reliable and consistent guidance for the titration of sedation depth.

The benefits of BIS monitoring of patients under general anaesthesia for surgical procedures have already been confirmed by another Cochrane review. By undertaking a well‐conducted systematic review our aim was to find out if BIS monitoring improves outcomes in mechanically ventilated adult intensive care unit (ICU) patients.

Objectives:  To assess the effects of BIS monitoring compared with clinical sedation assessment on ICU length of stay (LOS), duration of mechanical ventilation, any cause mortality, risk of ventilator‐associated pneumonia (VAP), risk of adverse events (e.g. self‐extubation, unplanned disconnection of indwelling catheters), hospital LOS, amount of sedative agents used, cost, longer‐term functional outcomes and quality of life as reported by authors for mechanically ventilated adults in the ICU.

Search methods:  We searched CENTRAL, MEDLINE, Embase, CINAHL, ProQuest, OpenGrey and SciSearch up to May 2017 and checked references citation searching and contacted study authors to identify additional studies. We searched trial registries, which included and controlled‐

Selection criteria:  We included all randomized controlled trials comparing BIS versus clinical assessment (CA) for the management of sedation in mechanically ventilated critically ill adults.

Data collection and analysis:  We used Cochrane’s standard methodological procedures. We undertook analysis using Revman 5.3 software.

Main results:  We identified 4245 possible studies from the initial search. Of those studies, four studies (256 participants) met the inclusion criteria. One more study is awaiting classification. Studies were, conducted in single‐centre surgical and mixed medical‐surgical ICUs. BIS monitor was used to assess the level of sedation in the intervention arm in all the studies. In the control arm, the sedation assessment tools for CA included the Sedation‐Agitation Scale (SAS), Ramsay Sedation Scale (RSS) or subjective CA utilizing traditional clinical signs (heart rate, blood pressure, conscious level and pupillary size). Only one study was classified as low risk of bias, the other three studies were classified as high risk.

There was no evidence of a difference in one study (N = 50) that measured ICU LOS (Median (Interquartile Range IQR) 8 (4 to 14) in the CA group; 12 (6 to 18) in the BIS group; low‐quality evidence).There was little or no effect on the duration of mechanical ventilation (MD ‐0.02 days (95% CI ‐0.13 to 0.09; 2 studies; N = 155; I2 = 0%; low‐quality evidence)). Adverse events were reported in one study (N = 105) and the effects on restlessness after suction, endotracheal tube resistance, pain tolerance during sedation or delirium after extubation were uncertain due to very low‐quality evidence. Clinically relevant adverse events such as self‐extubation were not reported in any study. Three studies reported the amount of sedative agents used. We could not measure combined difference in the amount of sedative agents used because of different sedation protocols and sedative agents used in the studies. GRADE quality of evidence was very low. No study reported other secondary outcomes of interest for the review.

Authors’ conclusions:  We found insufficient evidence about the effects of BIS monitoring for sedation in critically ill mechanically ventilated adults on clinical outcomes or resource utilization. The findings are uncertain due to the low‐ and very low‐quality evidence derived from a limited number of studies.

The full text of the review can be found via this link.

High‐flow nasal cannulae for respiratory support in adult intensive care patients

This systematic review produced by Corley and colleagues was published online in Cochrane Library in May 2017.

Backcochrane-57-1ground:  A common reason for intensive care unit (ICU) admission is the need for breathing (or respiratory) support. HFNC are small plastic tubes that sit inside the nostrils and deliver a heated mix of air and oxygen at high flow rates to patients requiring breathing support. They are used frequently in the ICU, yet no clear evidence shows whether they provide patients with long-term benefits such as reduced ICU stay or improved chances of survival.

Study characteristics:  The evidence is current to March 2016. We included in the review 11 studies with 1972 participants. Most participants had respiratory failure, or had just been taken off an artificial breathing machine. Included studies compared HFNC with low-flow oxygen given through face masks, through low-flow cannulae, or through devices that use mild pressure to aid oxygen delivery. We reran the search in December 2016 and will deal with any studies of interest when we update the review.

Key results:  We found no evidence that HFNC reduced the rate of treatment failure or risk of death compared with low-flow oxygen devices. We found no evidence of any advantages for HFNC in terms of adverse event rates, ICU length of stay, or duration of respiratory support. We observed no differences in participants’ blood oxygen levels or carbon dioxide blood levels, and we noted that any differences in breathing rates were small and were not considered clinically important. Studies reported no differences in patient-rated measures of comfort. Only one study found evidence of less dry mouth when HFNC was used.

Quality of evidence:  Most studies had reported methods inadequately, and we did not know whether risk of bias may have affected study results. We identified few eligible studies and noted some differences among participants within our included studies, particularly in reasons for requiring respiratory support. We used the GRADE system to rate the evidence for each of our outcomes, and we judged all evidence to be of low or very low quality.

Conclusion:  We were not able to collect sufficient evidence from good quality studies to determine whether HFNC offer a safe and effective way of delivering respiratory support for adults in the ICU.

The full text of the review can be accessed via this link to the Cochrane Library.

Effectiveness and safety of procalcitonin evaluation for reducing mortality in adults with sepsis, severe sepsis or septic shock

This systematic review by Andriolo et al was published in the Cochrane Library in January 2017.  The text below is the plain language summary with the full text available via this link.

Review question:  Is procalcitonin evaluation effective in reducing mortality and time receiving antimicrobial therapy in adults with sepsis?cochrane-57-1

Background:  Sepsis is defined as confirmed or suspected infection associated with a systemic inflammatory response syndrome (SIRS). This condition can evolve to an acute organ dysfunction, known as ‘severe sepsis’; or to persistent hypotension, even after adequate fluid replacement, known as ‘septic shock’. Procalcitonin (PCT) is a biological indicator in the blood that has been found to increase during blood infection. We wanted to assess whether evaluation of PCT can reduce mortality and time receiving antimicrobial therapy in adults with blood infection. To this end, we compared PCT versus nothing, versus standard care (only usual clinical judgement) and versus other blood chemical indicators. Nowadays, other chemical indicators include C-reactive protein (CRP), interleukins and neopterin.

Study characteristics:  The evidence is current to July 2015. However, we reran the search in October 2016 and will incorporate the three studies of interest when we update the review. For this version, we included 10 studies in this review. These studies were carried out in Australia, Brazil, China, Czech Republic, France, Germany, Indonesia and Switzerland. Researchers evaluated participants from academic and non-academic surgical, general and trauma intensive care units (ICUs) and emergency departments. All studies analysed adults with confirmed or presumed blood infection. Comparisons were most commonly based on ‘standard care’, but one trial used CRP-guided antibiotic therapy. In six trials, study authors had worked as consultants for, and/or received payments from, companies involved in the procalcitonin analysis.

Key results:  Results showed no significant differences in mortality at longest follow-up (124/573; 21.6% versus 152/583; 26.1%), at 28 days (37/160; 23.1% versus 39/156; 25%), at ICU discharge (28/247; 11.3% versus 25/259; 9.6%) or at hospital discharge (82/398; 20.6% versus 81/407; 19.9%), respectively, for PCT and non-PCT groups. Also, researchers found no differences in mechanical ventilation, clinical severity, reinfection or duration of antimicrobial therapy. No study provided information about participants for whom the antimicrobial regimen was changed from a broad to a narrower spectrum.

Quality of the evidence:  We considered the body of available evidence as having very low to moderate quality owing to absence of methods to prevent errors during studies or absence of information about such methods, as well as possibly insufficient numbers of studies and patients per outcome. Additionally, the authors of most studies worked as consultants and/or received payments from companies involved in the procalcitonin analysis.

Progesterone for acute traumatic brain injury

This systematic review by Ma et al was published in the Cochrane Library in December 2016.  The text below is the plain language summary with the full text available via this link.

Review question  To find out whether using the hormone progesterone to treat people who have had an injury to the head that caused brain damage (traumatic brain injury (TBI)) is helpful and safe, if given within 24 hours of the injury.
Background  TBI is one of the main causes of death and disability in people with injuries. Damage to the brain can start at the time of the injury, but can continue for days after the injury too. Progesterone is a hormone that some doctors think could be used as a potential medicine for reducing brain damage if given shortly after TBI. However, as there is uncertainty about the effectiveness of this hormone, it is important that we assess the evidence.
Study characteristics  We searched the medical literature widely for randomised controlled trials that investigated the effects of progesterone in people with TBI up to 30 September 2016. Randomised controlled trials provide the most robust medical evidence. .
Key results:  We included five studies with a total of 2392 participants, and identified three ongoing studies. The studies all compared a group of participants who received progesterone within 24 hours of TBI against a group who received a pretend – or dummy – medicine (known as a placebo) that looked the same as the progesterone.  The results of our review did not find evidence that, when compared to placebo, progesterone could reduce death and disability in people with TBI. There were too few data available on the other outcomes that we were interested in (pressure inside the skull (intracranial pressure), blood pressure, body temperature and adverse events (harms)), for us to be able to analyse these in detail. However, although the information available shows no evidence of a difference in effect between the progesterone and control groups for intracranial pressure, blood pressure or body temperature, one study showed an increased level of an adverse event called phlebitis (inflammation in the vein) in the progesterone group, possibly because the progestreone was given into the vein through an intravascular infusion (‘drip’).
Quality of the evidence  We judged the quality of the evidence to be low for the data on risk of death, and moderate for the data on risk of disability. These judgements resulted from differences across studies, including different doses of progesterone and different time points for assessment of participants in the included studies. This means that we have limited confidence in the conclusions of this review.

Oxygen therapy for acute myocardial infarction

cochrane-57-1This updated systematic review by Cabello et al was published in the Cochrane Library in December 2016.  The text below is the plain language summary with the full text available via this link.

Background  Many people who are having a heart attack are routinely given oxygen to breathe.
Review question  We looked for the evidence to support this longstanding practice by searching for randomised controlled trials that compared the outcomes for people given oxygen versus normal air to breathe. We were primarily interested in seeing whether there was a difference in the number of people who died, but we also looked at whether administering oxygen reduced pain or other adverse outcomes.
Key results  We found five randomised controlled trials that compared people with suspected or proven heart attack who were given oxygen to a similar group of people who were given air (evidence is current to June 2016). These trials involved a total of 1173 participants, 32 of whom died. There were similar death rates in both groups, suggesting oxygen neither helps nor harms, but the trials are not big enough to know for sure. Moreover, it is possible that more heart muscle might be damaged in people given oxygen than in people given air.
Conclusion  Since there is no evidence whether the oxygen is good or harmful in this clinical condition, it is important to test oxygen in a big trial as soon as possible to be sure that this common treatment is doing more good than harm in people who are having a heart attack.

Antibiotics for ventilator-associated pneumonia: Cochrane Review

This review by Arthur et al was published on 20th October 2016.  The plain language summary is shown below.  Full details of the review can be found via this link.

Background.  Ventilators are machines that breathe for patients. The ventilator tube goes into the mouth and through the windpipe. Sometimes there are bacteria on the ventilator tube that infect the patient’s lungs, leading to a disease called ventilator-associated pneumonia. Ventilator-associated pneumonia can cause significant harmful effects, and can sometimes lead to death. When treating people with ventilator-associated pneumonia, doctors must decide which antibiotic therapy to prescribe, usually without knowing the particular type of bacterial infection. This decision is important because inappropriate initial treatment may increase risk of harmful effects and longer hospital stays.

Search date  We searched for studies to December 2015.

Study characteristics  We looked at studies involving adults aged over 18 years who were treated in intensive care units for ventilator-associated pneumonia and needed antibiotic treatment. We analysed 12 studies with 3571 participants.

Key results  All included studies looked at the use of one antibiotic treatment plan versus another, but these varied among studies. There was potential for bias because some studies did not report outcomes for all participants, and funding for many was provided by pharmaceutical companies and study authors were affiliated with these companies.

We used statistical techniques to evaluate our results. For single versus multiple antibiotics, we found no difference in rates of death or cure, or adverse events. For our comparison of combination therapies with optional adjunctives we were only able to analyse clinical cure for one the antibiotics Tigecycline and imipenem-cilastatin for which imipenem-cilastatin was found to have higher clinica cure. We also looked at carbapenem (antibiotics used to treat infections caused by multidrug-resistant bacteria) versus non-carbapenem treatment; we found no difference in death rate or adverse effects, but we found that carbapenems are associated with an increase in clinical cure.

Quality of evidence  We assessed evidence quality as moderate for most outcomes, and very low for clinical cure when single-antibiotic treatment was compared with multiple antibiotic therapy. We also found that evidence quality was low for adverse events when carbapenem was compared with non-carbapenem treatment.

Conclusions  We did not find differences between single and combination therapy, lending support to use of a single-antibiotic treatment plan for people with ventilator-associated pneumonia. This may not be applicable to all patients because studies did not identify patients who are at risk of exposure to harmful types of bacteria.

We could not evaluate the best single-antibiotic choice to treat people with ventilator-associated pneumonia because there were too few studies, but carbapenems may achieve better cure rates than other tested antibiotics.