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.

Plasma transfusions prior to insertion of central lines for people with abnormal coagulation

Thcochrane-57-1is was published in the Cochrane Database of Systematic Reviews in September 2016.  The full text of this review is available via this link

Review question.  We evaluated the evidence about whether people with abnormal coagulation (poor blood clotting) require a plasma transfusion prior to insertion of a central line (central venous catheter (CVC)), and if so, what is the degree of abnormal coagulation at which a plasma transfusion is required.

Background  People with abnormal coagulation often require the insertion of central lines. Central lines are catheters whose tip usually lies in one of two main veins returning blood to the heart. They have a number of uses including: intensive monitoring and treatment of critically-ill patients; giving nutrition into a vein (when the patient cannot eat); giving chemotherapy or other irritant drugs with fewer complications; and when patients require long-term repeated treatments in to a vein. Current practice in many countries is to give plasma transfusions to prevent serious bleeding due to the procedure if blood tests to assess clotting are abnormal. The risk of bleeding after a central line insertion appears to be low if the clinician uses ultrasound to guide insertion of the line. Correction of clotting abnormalities with fresh frozen plasma (FFP) is not without risks of its own, and it is unclear whether this practice is beneficial or harmful. People may be exposed to the risks of a plasma transfusion without any obvious clinical benefit.

Study characteristics  The evidence is current to March 2016. In this review we identified four randomised controlled trials, three trials are still recruiting participants and are due to complete recruitment by February 2018. The completed trial (58 participants) compared plasma transfusion to no plasma transfusion prior to central line insertion.

Key results  There was not enough evidence to determine whether plasma transfusions affected minor or major procedure-related bleeding. The included study did not report the number of people dying due to any cause, the number of people receiving red cell or plasma transfusions, the occurrence of transfusion or line-related complications, length of time in hospital, correction of clotting abnormalities, or quality of life.

Quality of the evidence  The quality of the evidence is very low because this review includes only one small study.

Authors’ conclusions:  There is only very limited evidence from one RCT to inform the decision whether or not to administer prophylactic plasma prior to central venous catheterisation for people with abnormal coagulation. It is not possible from the current RCT evidence to recommend whether or not prophylactic plasma transfusion is beneficial or harmful in this situation. The three ongoing RCTs will not be able to answer this review’s questions, because they are small studies and do not address all of the comparisons included in this review (355 participants in total). To detect an increase in the proportion of participants who had major bleeding from 1 in 100 to 2 in 100 would require a study containing at least 4634 participants (80% power, 5% significance).