Prescribed hypocaloric nutrition support for critically‐ill adults

This Cochrane Systematic Review by Perman and colleagues was published in June 2018.  The full text of the systematic review is available via this link.

Background:  There are controversies about the amount of calories and thecochrane-57-1 type of nutritional support that should be given to critically‐ill people. Several authors advocate the potential benefits of hypocaloric nutrition support, but the evidence is inconclusive.

Objectives:  To assess the effects of prescribed hypocaloric nutrition support in comparison with standard nutrition support for critically‐ill adults.

Search methods:  We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Cochrane Library), MEDLINE, Embase and LILACS (from inception to 20 June 2017) with a specific strategy for each database. We also assessed three websites, conference proceedings and reference lists, and contacted leaders in the field and the pharmaceutical industry for undetected/unpublished studies. There was no restriction by date, language or publication status.
Selection criteria:  We included randomized and quasi‐randomized controlled trials comparing hypocaloric nutrition support to normo‐ or hypercaloric nutrition support or no nutrition support (e.g. fasting) in adults hospitalized in intensive care units (ICUs).
Data collection and analysis:  We used standard methodological procedures expected by Cochrane. We meta‐analysed data for comparisons in which clinical heterogeneity was low. We conducted pre-specified subgroup and sensitivity analyses, and post hoc analyses, including meta‐regression. Our primary outcomes were: mortality (death occurred during the ICU and hospital stay, or 28‐ to 30‐day all‐cause mortality); length of stay (days stayed in the ICU and in the hospital); and Infectious complications. Secondary outcomes included: length of mechanical ventilation. We assessed the quality of evidence with GRADE.
Main results:  We identified 15 trials, with a total of 3129 ICU participants from university‐associated hospitals in the USA, Colombia, Saudi Arabia, Canada, Greece, Germany and Iran. There are two ongoing studies. Participants suffered from medical and surgical conditions, with a variety of inclusion criteria. Four studies used parenteral nutrition and nine studies used only enteral nutrition; it was unclear whether the remaining two used parenteral nutrition. Most of them could not achieve the proposed caloric targets, resulting in small differences in the administered calories between intervention and control groups. Most studies were funded by the US government or non‐governmental associations, but three studies received funding from industry. Five studies did not specify their funding sources.
The included studies suffered from important clinical and statistical heterogeneity. This heterogeneity did not allow us to report pooled estimates of the primary and secondary outcomes, so we have described them narratively.
When comparing hypocaloric nutrition support with a control nutrition support, for hospital mortality (9 studies, 1775 participants), the risk ratios ranged from 0.23 to 5.54; for ICU mortality (4 studies, 1291 participants) the risk ratios ranged from 0.81 to 5.54, and for mortality at 30 days (7 studies, 2611 participants) the risk ratios ranged from 0.79 to 3.00. Most of these estimates included the null value. The quality of the evidence was very low due to unclear or high risk of bias, inconsistency and imprecision.
Participants who received hypocaloric nutrition support compared to control nutrition support had a range of mean hospital lengths of stay of 15.70 days lower to 10.70 days higher (10 studies, 1677 participants), a range of mean ICU lengths of stay 11.00 days lower to 5.40 days higher (11 studies, 2942 participants) and a range of mean lengths of mechanical ventilation of 13.20 days lower to 8.36 days higher (12 studies, 3000 participants). The quality of the evidence for this outcome was very low due to unclear or high risk of bias in most studies, inconsistency and imprecision.

The risk ratios for infectious complications (10 studies, 2804 participants) of each individual study ranged from 0.54 to 2.54. The quality of the evidence for this outcome was very low due to unclear or high risk of bias, inconsistency and imprecision.
We were not able to explain the causes of the observed heterogeneity using subgroup and sensitivity analyses or meta‐regression.

Authors’ conclusions:  The included studies had substantial clinical heterogeneity. We found very low‐quality evidence about the effects of prescribed hypocaloric nutrition support on mortality in hospital, in the ICU and at 30 days, as well as in length of hospital and ICU stay, infectious complications and the length of mechanical ventilation. For these outcomes there is uncertainty about the effects of prescribed hypocaloric nutrition, since the range of estimates includes both appreciable benefits and harms.

Given these limitations, results must be interpreted with caution in the clinical field, considering the unclear balance of the risks and harms of this intervention. Future research addressing the clinical heterogeneity of participants and interventions, study limitations and sample size could clarify the effects of this intervention.

Advertisements

Automated monitoring compared to standard care for the early detection of sepsis in critically ill patients

This Cochrane Systematic Review by Warttig and colleagues was published in June 2018.  The full text of the systematic review is available via this link.
Background:  Sepsis is a life‐threatening condition that is usually diagnosed when a patient has a suspected or documented infection, and meets two or more criteria for systemic inflammatory response syndrcochrane-57-1ome (SIRS). The incidence of sepsis is higher among people admitted to critical care settings such as the intensive care unit (ICU) than among people in other settings. If left untreated sepsis can quickly worsen; severe sepsis has a mortality rate of 40% or higher, depending on definition. Recognition of sepsis can be challenging as it usually requires patient data to be combined from multiple unconnected sources, and interpreted correctly, which can be complex and time consuming to do. Electronic systems that are designed to connect information sources together, and automatically collate, analyse, and continuously monitor the information, as well as alerting healthcare staff when pre‐determined diagnostic thresholds are met, may offer benefits by facilitating earlier recognition of sepsis and faster initiation of treatment, such as antimicrobial therapy, fluid resuscitation, inotropes, and vasopressors if appropriate. However, there is the possibility that electronic, automated systems do not offer benefits, or even cause harm. This might happen if the systems are unable to correctly detect sepsis (meaning that treatment is not started when it should be, or it is started when it shouldn’t be), or healthcare staff may not respond to alerts quickly enough, or get ‘alarm fatigue’ especially if the alarms go off frequently or give too many false alarms.

Objectives:  To evaluate whether automated systems for the early detection of sepsis can reduce the time to appropriate treatment (such as initiation of antibiotics, fluids, inotropes, and vasopressors) and improve clinical outcomes in critically ill patients in the ICU.

Search methods:  We searched CENTRAL; MEDLINE; Embase; CINAHL; ISI Web of science; and LILACS, clinicaltrials.gov, and the World Health Organization trials portal. We searched all databases from their date of inception to 18 September 2017, with no restriction on country or language of publication.
Selection criteria:  We included randomized controlled trials (RCTs) that compared automated sepsis‐monitoring systems to standard care (such as paper‐based systems) in participants of any age admitted to intensive or critical care units for critical illness. We defined an automated system as any process capable of screening patient records or data (one or more systems) automatically at intervals for markers or characteristics that are indicative of sepsis. We defined critical illness as including, but not limited to postsurgery, trauma, stroke, myocardial infarction, arrhythmia, burns, and hypovolaemic or haemorrhagic shock. We excluded non‐randomized studies, quasi‐randomized studies, and cross‐over studies . We also excluded studies including people already diagnosed with sepsis.
Data collection and analysis:  We used the standard methodological procedures expected by Cochrane. Our primary outcomes were: time to initiation of antimicrobial therapy; time to initiation of fluid resuscitation; and 30‐day mortality. Secondary outcomes included: length of stay in ICU; failed detection of sepsis; and quality of life. We used GRADE to assess the quality of evidence for each outcome.

Main results:  We included three RCTs in this review. It was unclear if the RCTs were three separate studies involving 1199 participants in total, or if they were reports from the same study involving fewer participants. We decided to treat the studies separately, as we were unable to make contact with the study authors to clarify.
All three RCTs are of very low study quality because of issues with unclear randomization methods, allocation concealment and uncertainty of effect size. Some of the studies were reported as abstracts only and contained limited data, which prevented meaningful analysis and assessment of potential biases.
The studies included participants who all received automated electronic monitoring during their hospital stay. Participants were randomized to an intervention group (automated alerts sent from the system) or to usual care (no automated alerts sent from the system).
Evidence from all three studies reported ‘Time to initiation of antimicrobial therapy’. We were unable to pool the data, but the largest study involving 680 participants reported median time to initiation of antimicrobial therapy in the intervention group of 5.6 hours (interquartile range (IQR) 2.3 to 19.7) in the intervention group (n = not stated) and 7.8 hours (IQR 2.5 to 33.1) in the control group (n = not stated).
No studies reported ‘Time to initiation of fluid resuscitation’ or the adverse event ‘Mortality at 30 days’. However very low‐quality evidence was available where mortality was reported at other time points. One study involving 77 participants reported 14‐day mortality of 20% in the intervention group and 21% in the control group (numerator and denominator not stated). One study involving 442 participants reported mortality at 28 days, or discharge was 14% in the intervention group and 10% in the control group (numerator and denominator not reported). Sample sizes were not reported adequately for these outcomes and so we could not estimate confidence intervals.

Very low‐quality evidence from one study involving 442 participants reported ‘Length of stay in ICU’. Median length of stay was 3.0 days in the intervention group (IQR = 2.0 to 5.0), and 3.0 days (IQR 2.0 to 4.0 in the control).
Very low‐quality evidence from one study involving at least 442 participants reported the adverse effect ‘Failed detection of sepsis’. Data were only reported for failed detection of sepsis in two participants and it wasn’t clear which group(s) this outcome occurred in.
No studies reported ‘Quality of life’.
Authors’ conclusions:  It is unclear what effect automated systems for monitoring sepsis have on any of the outcomes included in this review. Very low‐quality evidence is only available on automated alerts, which is only one component of automated monitoring systems. It is uncertain whether such systems can replace regular, careful review of the patient’s condition by experienced healthcare staff.

Automated monitoring for the early detection of sepsis in patients receiving care in intensive care units

Review question:  Can automated systems for the early detection of sepsis reduce the time to treatment and improve outcomes in patients in the intensive care unit (ICU), in comparison to standard care?
cochrane-57-1Background:  Sepsis happens when a person develops an infection and their immune system overreacts to it. If sepsis is not managed it can quickly develop into septic shock, which causes organs such as the liver and heart to stop working properly. People can be affected by sepsis at any time but people in intensive care settings are more likely to be affected by it. Septic shock is fatal for 20% to 70% of people admitted to intensive care in Europe. There is no single diagnostic test that can tell if someone has sepsis or not. Instead, the results of several tests (such as blood tests) have to be reviewed along with other information about the patient (such as their medical history), and clinical observations (such as heart rate, temperature, and blood pressure). This process can be time consuming and complicated to do. People already admitted to intensive care are likely to be very unwell and it can be difficult to tell if abnormal results are because of the problem that caused them to be admitted to intensive care, or because of sepsis.
Automated monitoring systems are electronic systems that can collect and analyse information from different sources, and can be used to alert staff when the signs and symptoms of sepsis have been identified. This may mean that sepsis is diagnosed at the earliest possible time, enabling treatment to begin before organ damage happens. However, there is the possibility that automated monitoring systems don’t help, or even cause harm. This might happen if the systems are unable to correctly detect sepsis (meaning that treatment is not started when it should be, or it is started when it shouldn’t be), or health care staff may not respond to alerts quickly enough, especially if the systems give too many false alarms.
Study characteristics:  We conducted a search to identify evidence published before September 2017. Studies were eligible for inclusion if they compared automated sepsis monitoring to standard care (such as paper‐based systems) in people admitted to intensive or critical care units for critical illness. We did not include non‐randomized studies (studies where participants were not allocated to treatment groups by chance), quasi‐randomized studies (studies where participants were allocated to treatment groups by a method that is not truly down to chance, such as date of birth or medical number), and cross‐over studies (where participants first receive one treatment and then cross over to receive the other treatment). Studies including people already diagnosed with sepsis were also excluded.
Key results:  We included three randomized controlled trials (studies where participants were allocated to treatment groups by chance), involving 1199 participants in this review. Overall there were no significant differences in time to start of antimicrobial therapy (such as antimicrobial and antifungal treatments, very low‐quality evidence), length of stay in the intensive care setting (very low‐quality evidence), or in mortality at 14 days, 28 days or discharge (very low‐quality evidence) when automated monitoring systems were compared to standard care. Very low‐quality evidence was available on failed detection of sepsis but data reporting was too unclear to enable us to analyse this in a meaningful way. Other outcomes that we wished to assess like time to initiation of fluid resuscitation (the process of increasing the amount of fluids in the body), mortality at 30 days, and quality of life were not reported in any of the studies.
Quality of the evidence:  Results of this review show limited, very low‐quality evidence, which has prevented us from drawing meaningful conclusions. It is unclear what effect automated systems for monitoring sepsis have on any outcomes included in this review, and therefore we are uncertain if automated sepsis monitoring is beneficial or not. Additional, high‐quality evidence is needed to help address our review question.
The full text of this Cochrane Review is freely available via this link.

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 clinicaltrials.gov and controlled‐trials.com.

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.