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Critical Care (London, England) Jan 2021Acute kidney injury (AKI) is a common serious complication in critically ill patients. AKI occurs in up to 50% patients in intensive care unit (ICU), with poor clinical... (Meta-Analysis)
Meta-Analysis
Timing of renal replacement therapy initiation for acute kidney injury in critically ill patients: a systematic review of randomized clinical trials with meta-analysis and trial sequential analysis.
BACKGROUND
Acute kidney injury (AKI) is a common serious complication in critically ill patients. AKI occurs in up to 50% patients in intensive care unit (ICU), with poor clinical prognosis. Renal replacement therapy (RRT) has been widely used in critically ill patients with AKI. However, in patients without urgent indications such as acute pulmonary edema, severe acidosis, and severe hyperkalemia, the optimal timing of RRT initiation is still under debate. We conducted this systematic review of randomized clinical trials (RCTs) with meta-analysis and trial sequential analysis (TSA) to compare the effects of early RRT initiation versus delayed RRT initiation.
METHODS
We searched databases (PubMed, EMBASE and Cochrane Library) from inception through to July 20, 2020, to identify eligible RCTs. The primary outcome was 28-day mortality. Two authors extracted the data independently. When the I values < 25%, we used fixed-effect mode. Otherwise, the random effects model was used as appropriate. TSA was performed to control the risk of random errors and assess whether the results in our meta-analysis were conclusive.
RESULTS
Eleven studies involving 5086 patients were identified. Two studies included patients with sepsis, one study included patients with shock after cardiac surgery, and eight others included mixed populations. The criteria for the initiation of RRT, the definition of AKI, and RRT modalities existed great variations among the studies. The median time of RRT initiation across studies ranged from 2 to 7.6 h in the early RRT group and 21 to 57 h in the delayed RRT group. The pooled results showed that early initiation of RRT could not decrease 28-day all-cause mortality compared with delayed RRT (RR 1.01; 95% CI 0.94-1.09; P = 0.77; I = 0%). TSA result showed that the required information size was 2949. The cumulative Z curve crossed the futility boundary and reached the required information size. In addition, early initiation of RRT could lead to unnecessary RRT exposure in some patients and was associated with a higher incidence of hypotension (RR 1.42; 95% CI 1.23-1.63; P < 0.00001; I = 8%) and RRT-associated infection events (RR 1.34; 95% CI 1.01-1.78; P = 0.04; I = 0%).
CONCLUSIONS
This meta-analysis suggested that early initiation of RRT was not associated with survival benefit in critically ill patients with AKI. In addition, early initiation of RRT could lead to unnecessary RRT exposure in some patients, resulting in a waste of health resources and a higher incidence of RRT-associated adverse events. Maybe, only critically ill patients with a clear and hard indication, such as severe acidosis, pulmonary edema, and hyperkalemia, could benefit from early initiation of RRT.
Topics: Acute Kidney Injury; Critical Illness; Humans; Incidence; Randomized Controlled Trials as Topic; Renal Replacement Therapy; Time Factors; Time-to-Treatment
PubMed: 33407756
DOI: 10.1186/s13054-020-03451-y -
Anesthesia and Analgesia Apr 2021Laryngeal injury from intubation can substantially impact airway, voice, and swallowing, thus necessitating multidisciplinary interventions. The goals of this systematic... (Meta-Analysis)
Meta-Analysis
Laryngeal injury from intubation can substantially impact airway, voice, and swallowing, thus necessitating multidisciplinary interventions. The goals of this systematic review were (1) to review the types of laryngeal injuries and their patient-reported symptoms and clinical signs resulting from endotracheal intubation in patients intubated for surgeries and (2) to better understand the overall the frequency at which these injuries occur. We conducted a search of 4 online bibliographic databases (ie, PubMed, Embase, Cumulative Index of Nursing and Allied Health Literature [CINAHL], and The Cochrane Library) and ProQuest and Open Access Thesis Dissertations (OPTD) from database inception to September 2019 without restrictions for language. Studies that completed postextubation laryngeal examinations with visualization in adult patients who were endotracheally intubated for surgeries were included. We excluded (1) retrospective studies, (2) case studies, (3) preexisting laryngeal injury/disease, (4) patients with histories of or surgical interventions that risk injury to the recurrent laryngeal nerve, (5) conference abstracts, and (6) patient populations with nonfocal, neurological impairments that may impact voice and swallowing function, thus making it difficult to identify isolated postextubation laryngeal injury. Independent, double-data extraction, and risk of bias assessment followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Cochrane Collaboration's criteria. Twenty-one articles (1 cross-sectional, 3 cohort, 5 case series, 12 randomized controlled trials) representing 21 surgical studies containing 6140 patients met eligibility criteria. The mean patient age across studies reporting age was 49 (95% confidence interval [CI], 45-53) years with a mean intubation duration of 132 (95% CI, 106-159) minutes. Studies reported no injuries in 80% (95% CI, 69-88) of patients. All 21 studies presented on type of injury. Edema was the most frequently reported mild injury, with a prevalence of 9%-84%. Vocal fold hematomas were the most frequently reported moderate injury, with a prevalence of 4% (95% CI, 2-10). Severe injuries that include subluxation of the arytenoids and vocal fold paralysis are rare (<1%) outcomes. The most prevalent patient complaints postextubation were dysphagia (43%), pain (38%), coughing (32%), a sore throat (27%), and hoarseness (27%). Overall, laryngeal injury from short-duration surgical intubation is common and is most often mild. No uniform guidelines for laryngeal assessment postextubation from surgery are available and hoarseness is neither a good indicator of laryngeal injury or dysphagia. Protocolized screening for dysphonia and dysphagia postextubation may lead to improved identification of injury and, therefore, improved patient outcomes and reduced health care utilization.
Topics: Airway Extubation; Anesthesia; Female; Humans; Intubation, Intratracheal; Larynx; Male; Middle Aged; Postoperative Complications; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 33196479
DOI: 10.1213/ANE.0000000000005276 -
Cytokine Jan 2021COVID-19, as a newly-emerged viral infection has now spread all over the world after originating in Wuhan, China. Pneumonia is the hallmark of the disease, with dyspnea...
BACKGROUND
COVID-19, as a newly-emerged viral infection has now spread all over the world after originating in Wuhan, China. Pneumonia is the hallmark of the disease, with dyspnea in half of the patients and acute respiratory distress syndrome (ARDS) in up to one -third of the cases. Pulmonary edema, neutrophilic infiltration, and inflammatory cytokine release are the pathologic signs of this disease. The anti-inflammatory effect of the photobiomodulation (PBM) has been confirmed in many previous studies. Therefore, this review study was conducted to evaluate the direct effect of PBM on the acute lung inflammation or ARDS and also accelerating the regeneration of the damaged tissues. The indirect effects of PBM on modulation of the immune system, increasing the blood flow and oxygenation in other tissues were also considered.
METHODOLOGY
The databases of PubMed, Cochrane library, and Google Scholar were searched to find the relevant studies. Keywords included the PBM and related terms, lung inflammation, and COVID-19 -related signs. Studies were categorized with respect to the target tissue, laser parameters, and their results.
RESULTS
Seventeen related papers were included in this review. All of them were in animal models. They showed that the PBM could significantly decrease the pulmonary edema, neutrophil influx, and generation of pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), intracellular adhesion molecule (ICAM), reactive oxygen species (ROS), isoform of nitric oxide synthase (iNOS), and macrophage inflammatory protein 2 (MIP-2)).
CONCLUSION
Our findings revealed that the PBM could be helpful in reducing the lung inflammation and promoting the regeneration of the damaged tissue. PBM can increase the oxygenation indirectly in order to rehabilitate the affected organs. Thus, the infra-red lasers or light-emitting diodes (LEDs) are recommended in this regard.
Topics: COVID-19; Cytokines; Humans; Low-Level Light Therapy; Lung; Macrophages; Neutrophils; Pneumonia; PubMed; Pulmonary Edema; Reactive Oxygen Species; Respiratory Distress Syndrome
PubMed: 33128927
DOI: 10.1016/j.cyto.2020.155312 -
Perioperative Medicine (London, England) 2020Perioperative goal-directed haemodynamic therapy (GDHT), defined as the administration of fluids with or without inotropes or vasoactive agents against explicit measured...
BACKGROUND
Perioperative goal-directed haemodynamic therapy (GDHT), defined as the administration of fluids with or without inotropes or vasoactive agents against explicit measured goals to augment blood flow, has been evaluated in many randomised controlled trials (RCTs) over the past four decades. Reported post-operative pulmonary complications commonly include chest infection or pneumonia, atelectasis, acute respiratory distress syndrome or acute lung injury, aspiration pneumonitis, pulmonary embolism, and pulmonary oedema. Despite the substantial clinical literature in this area, it remains unclear whether their incidence is reduced by GDHT. This systematic review aims to determine the effect of GDHT on the respiratory outcomes listed above, in surgical patients.
METHODS
We searched the Cochrane Central Register for Controlled Trials (CENTRAL), MEDLINE, EMBASE, and clinical trial registries up until January 2020. We included all RCTs reporting pulmonary outcomes. The primary outcome was post-operative pulmonary complications and secondary outcomes were specific pulmonary complications and intra-operative fluid input. Data synthesis was performed on Review Manager and heterogeneity was assessed using statistics.
RESULTS
We identified 66 studies with 9548 participants reporting pulmonary complications. GDHT resulted in a significant reduction in total pulmonary complications (OR 0.74, 95% CI 0.59 to 0.92). The incidence of pulmonary infections, reported in 45 studies with 6969 participants, was significantly lower in the GDHT group (OR 0.72, CI 0.60 to 0.86). Pulmonary oedema was recorded in 23 studies with 3205 participants and was less common in the GDHT group (OR 0.47, CI 0.30 to 0.73). There were no differences in the incidences of pulmonary embolism or acute respiratory distress syndrome. Sub-group analyses demonstrated: (i) benefit from GDHT in general/abdominal/mixed and cardiothoracic surgery but not in orthopaedic or vascular surgery; and (ii) benefit from fluids with inotropes and/or vasopressors in combination but not from fluids alone. Overall, the GDHT group received more colloid (+280 ml) and less crystalloid (-375 ml) solutions than the control group. Due to clinical and statistical heterogeneity, we downgraded this evidence to moderate.
CONCLUSIONS
This systematic review and meta-analysis suggests that the use of GDHT using fluids with inotropes and/or vasopressors, but not fluids alone, reduces the development of post-operative pulmonary infections and pulmonary oedema in general, abdominal and cardiothoracic surgical patients. This evidence was graded as moderate.PROSPERO registry reference: CRD42020170361.
PubMed: 33072306
DOI: 10.1186/s13741-020-00161-5 -
Healthcare (Basel, Switzerland) Sep 2020Scorpion sting is a public health issue in several countries, particularly in America, the Middle East, India and Africa. The estimated annual global incidence of... (Review)
Review
Scorpion sting is a public health issue in several countries, particularly in America, the Middle East, India and Africa. The estimated annual global incidence of scorpion envenomings is about 1.5 million, resulting in 2600 deaths. Scorpions are Arthropoda characterized by a tail ending in a terminal bulbous (telson) containing paired venom glands and the stinger. There are 19 known families of scorpions and more than 2200 species, of which about 50 from the families of Buthidae, Hemiscorpiidae and Scorpionidae are harmful to humans. Scorpion venom is a complex structure composed of neurotoxic proteins, salts, acidic proteins and organic compounds, thereby having neurologic, cardiovascular, hematologic and renal side effects, in addition to local effects such as redness, pain, burning and swelling. When the sting is fatal, the mechanism of death is often related to cardiotoxicity with terminal pulmonary edema. However, the cholinergic excess or the neuromuscular excitation can provoke respiratory failure. Sometimes, death is due to an anaphylactic reaction to the envenoming. The purpose of this literature review is to evaluate the autopsy findings in scorpion sting-related deaths in order to better understand the pathophysiological mechanisms underlying them, thus helping pathologists in defining the correct diagnosis.
PubMed: 32899951
DOI: 10.3390/healthcare8030325 -
Headache Sep 2020To summarize the current literature on non-steroidal anti-inflammatory drug and corticosteroid use during the coronavirus disease 2019 (COVID-19) pandemic, recognizing...
OBJECTIVE
To summarize the current literature on non-steroidal anti-inflammatory drug and corticosteroid use during the coronavirus disease 2019 (COVID-19) pandemic, recognizing that these are commonly used treatments in the field of headache medicine.
BACKGROUND
The use of non-steroidal anti-inflammatory drugs and corticosteroids in patients during the COVID-19 pandemic has been a controversial topic within the medical community and international and national health organizations. Lay press and social media outlets have circulated opinions on this topic despite the fact that the evidence for or against the use of these medications is sparse. In the field of headache medicine, these medications are used commonly and both patients and clinicians may have questions or hesitations pertaining to their use during the COVID-19 pandemic.
METHODS
A detailed search of the scientific and popular literature was performed.
RESULTS
There is limited literature pertaining to the safety of non-steroidal anti-inflammatory drugs and corticosteroids during the COVID-19 pandemic. To date, there are no clear scientific data that preclude the use of non-steroidal anti-inflammatory drugs in the general population who may acquire COVID-19 or in those acutely infected with the virus. Several health organizations have concluded that treatment with corticosteroids during active infection should be avoided due to concerns of prolonged viral shedding in the respiratory tract and the lack of survival benefit based on the data from past coronaviruses and influenza virus; specific exceptions exist including treatment for underlying asthma or chronic obstructive pulmonary disease, septic shock, and acute respiratory distress syndrome.
CONCLUSION
Scientific information regarding the COVID-19 pandemic is constantly evolving, and limited or contradictory information can lead to confusion for both patients and clinicians. It is recommended that prior to prescribing non-steroidal anti-inflammatory drugs and steroids for the treatment of headache, clinicians have open discussions with their patients about the potential risks and benefits of using these medications during the COVID-19 pandemic. This manuscript summarizes the currently available evidence and understanding about these risks and benefits to help clinicians navigate such discussions.
Topics: Adrenal Cortex Hormones; Angiotensin-Converting Enzyme 2; Animals; Anti-Inflammatory Agents, Non-Steroidal; COVID-19; Contraindications, Drug; Disease Susceptibility; Dogs; Headache; Humans; Hypernatremia; Immunosuppressive Agents; Mass Media; Models, Animal; Neutrophils; Pandemics; Practice Guidelines as Topic; Pulmonary Edema; Rats; Receptors, Virus; Risk Assessment; SARS-CoV-2; Up-Regulation; Virus Shedding
PubMed: 32648592
DOI: 10.1111/head.13903 -
Current Cardiology Reviews 2021Pericardial Decompression Syndrome (PDS) is defined as paradoxical hemodynamic deterioration and/or pulmonary edema, commonly associated with ventricular dysfunction....
BACKGROUND
Pericardial Decompression Syndrome (PDS) is defined as paradoxical hemodynamic deterioration and/or pulmonary edema, commonly associated with ventricular dysfunction. This phenomenon was first described by Vandyke in 1983. PDS is a rare but formidable complication of pericardiocentesis, which, if not managed appropriately, is fatal. PDS, as an entity, has discrete literature; this review is to understand its epidemiology, presentation, and management.
METHODOLOGY
Medline, Science Direct and Google Scholar databases were utilized to do a systemic literature search. PRISMA protocol was employed. Abstracts, case reports, case series and clinical studies were identified from 1983 to 2019. A total of 6508 articles were reviewed, out of which, 210 were short-listed, and after removal of duplicates, 49 manuscripts were included in this review. For statistical analysis, patient data was tabulated in SPSS version 20. Cases were divided into two categories surgical and percutaneous groups. t-test was conducted for continuous variable and chi-square test was conducted for categorical data used for analysis.
RESULTS
A total of 42 full-length case reports, 2 poster abstracts, 3 case series of 2 patients, 1 case series of 4 patients and 1 case series of 5 patients were included in the study. A total of 59 cases were included in this manuscript. Our data had 45.8% (n=27) males and 54.2% (n=32) females. The mean age of patients was 48.04 ± 17 years. Pericardiocentesis was performed in 52.5% (n=31) cases, and pericardiostomy was performed in 45.8% (n=27). The most common identifiable cause of pericardial effusion was found to be malignancy in 35.6% (n=21). Twenty-three 23 cases reported pre-procedural ejection fraction, which ranged from 20%-75% with a mean of 55.8 ± 14.6%, while 26 cases reported post-procedural ejection fraction which ranged from 10%-65% with a mean of 30% ± 15.1%. Data was further divided into two categories, namely, pericardiocentesis and pericardiostomy. The outcome as death was significant in the pericardiostomy arm with a p-value of < 0.00. The use of inotropic agents for the treatment of PDS was more common in needle pericardiocentesis with a p-value of 0.04. Lastly, the computed recovery time did not yield any significance with a p-value of 0.275.
CONCLUSION
Pericardial decompression syndrome is a rare condition with high mortality. Operators performing pericardial drainage should be aware of this complication following drainage of cardiac tamponade, since early recognition and expeditious supportive care are the only therapeutic modalities available for adequate management of this complication.
Topics: Decompression; Female; Humans; Male; Pericardiocentesis; Syndrome
PubMed: 32515313
DOI: 10.2174/1573403X16666200607184501 -
Pharmacology Research & Perspectives Jun 2020This study aimed to investigate the short-term efficacy and safety of tolvaptan as an add-on to traditional diuretics in patients with acute heart failure (AHF). The... (Comparative Study)
Comparative Study Meta-Analysis
This study aimed to investigate the short-term efficacy and safety of tolvaptan as an add-on to traditional diuretics in patients with acute heart failure (AHF). The PubMed, EMBASE, Cochrane Library, and Web of Science databases were comprehensively searched for all randomized controlled trials (RCTs) that examined AHF patients treated with tolvaptan as a combination therapy with traditional diuretics published on or before December 2, 2019. Efficacy indicators such as improved dyspnea, reduced edema, and changes in urine output and body weight were evaluated. In-hospital mortality and worsening renal function (WRF) were measured as safety indicators. Data from the published literature included in this study were independently extracted by two reviewers. The Cochrane risk of bias tool was used to evaluate the quality of the included RCTs. Twelve RCTs involving 5577 patients admitted for AHF were included. Compared with traditional diuretics alone, add-on tolvaptan significantly relieved dyspnea, reduced weight, increased total urine volume and changes in urine volume from baseline, reduced edema, and increased serum sodium concentration in the short term without increasing the mortality. Most importantly, a low dose of tolvaptan (7.5-15 mg/d) significantly reduced the incidence of WRF, while a high dose (30 mg/d) had the opposite effect. Short-term add-on tolvaptan in hospitalized AHF patients could significantly relieve shortness of breath, reduce body weight, improve edema, and increase urine output and serum sodium concentrations without increasing mortality. The protective effects of add-on tolvaptan against WRF, however, were observed at low doses, but not at high doses.
Topics: Acute Disease; Antidiuretic Hormone Receptor Antagonists; Diuretics; Dose-Response Relationship, Drug; Drug Therapy, Combination; Heart Failure; Humans; Randomized Controlled Trials as Topic; Tolvaptan
PubMed: 32500625
DOI: 10.1002/prp2.614 -
The Cochrane Database of Systematic... Jan 2020Increased intracranial pressure has been shown to be strongly associated with poor neurological outcomes and mortality for patients with acute traumatic brain injury.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Increased intracranial pressure has been shown to be strongly associated with poor neurological outcomes and mortality for patients with acute traumatic brain injury. Currently, most efforts to treat these injuries focus on controlling the intracranial pressure. Hypertonic saline is a hyperosmolar therapy that is used in traumatic brain injury to reduce intracranial pressure. The effectiveness of hypertonic saline compared with other intracranial pressure-lowering agents in the management of acute traumatic brain injury is still debated, both in the short and the long term.
OBJECTIVES
To assess the comparative efficacy and safety of hypertonic saline versus other intracranial pressure-lowering agents in the management of acute traumatic brain injury.
SEARCH METHODS
We searched Cochrane Injuries' Specialised Register, CENTRAL, PubMed, Embase Classic+Embase, ISI Web of Science: Science Citation Index and Conference Proceedings Citation Index-Science, as well as trials registers, on 11 December 2019. We supplemented these searches with searches of four major Chinese databases on 19 September 2018. We also checked bibliographies, and contacted trial authors to identify additional trials.
SELECTION CRITERIA
We sought to identify all randomised controlled trials (RCTs) of hypertonic saline versus other intracranial pressure-lowering agents for people with acute traumatic brain injury of any severity. We excluded cross-over trials as incompatible with assessing long-term outcomes.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened search results to identify potentially eligible trials and extracted data using a standard data extraction form. Outcome measures included: mortality at end of follow-up (all-cause); death or disability (as measured by the Glasgow Outcome Scale (GOS)); uncontrolled intracranial pressure (defined as failure to decrease the intracranial pressure to target and/or requiring additional intervention); and adverse events e.g. rebound phenomena; pulmonary oedema; acute renal failure during treatment).
MAIN RESULTS
Six trials, involving data from 287 people, met the inclusion criteria. The majority of participants (91%) had a diagnosis of severe traumatic brain injury. We had concerns about particular domains of risk of bias in each trial, as physicians were not reliably blinded to allocation, two trials contained participants with conditions other than traumatic brain injury and in one trial, we had concerns about missing data for important outcomes. The original protocol was available for only one trial and other trials (where registered) were registered retrospectively. Meta-analysis for both the primary outcome (mortality at final follow-up) and for 'poor outcome' as per conventionally dichotomised GOS criteria, was only possible for two trials. Synthesis of long-term outcomes was inhibited by the fact that two trials ceased data collection within two hours of a single bolus dose of an intracranial pressure-lowering agent and one at discharge from the intensive care unit (ICU). Only three trials collected data after participants were released from hospital, one of which did not report mortality and reported a 'poor outcome' by GOS criteria in an unconventional way. Substantial missing data in a key trial meant that in meta-analysis we report 'best-case' and 'worst-case' estimates alongside available case analysis. In no scenario did we discern a clear difference between treatments for either mortality or poor neurological outcome. Due to variation in modes of drug administration (including whether it followed or did not follow cerebrospinal fluid (CSF) drainage, as well as different follow-up times and ways of reporting changes in intracranial pressure, as well as no uniform definition of 'uncontrolled intracranial pressure', we did not perform meta-analysis for this outcome and report results narratively, by individual trial. Trials tended to report both treatments to be effective in reducing elevated intracranial pressure but that hypertonic saline had increased benefits, usually adding that pretreatment factors need to be considered (e.g. serum sodium and both system and brain haemodynamics). No trial provided data for our other outcomes of interest. We consider evidence quality for all outcomes to be very low, as assessed by GRADE; we downgraded all conclusions due to imprecision (small sample size), indirectness (due to choice of measurement and/or selection of participants without traumatic brain injury), and in some cases, risk of bias and inconsistency. Only one of the included trials reported data on adverse effects; a rebound phenomenon, which was present only in the comparator group (mannitol). None of the trials reported data on pulmonary oedema or acute renal failure during treatment. On the whole, trial authors do not seem to have rigorously sought to collect data on adverse events.
AUTHORS' CONCLUSIONS
This review set out to find trials comparing hypertonic saline to a potential range of other intracranial pressure-lowering agents, but only identified trials comparing it with mannitol or mannitol in combination with glycerol. Based on limited data, there is weak evidence to suggest that hypertonic saline is no better than mannitol in efficacy and safety in the long-term management of acute traumatic brain injury. Future research should be comprised of large, multi-site trials, prospectively registered, reported in accordance with current best practice. Trials should investigate issues such as the type of traumatic brain injury suffered by participants and concentration of infusion and length of time over which the infusion is given.
Topics: Brain Injuries; Brain Injuries, Traumatic; Glasgow Outcome Scale; Humans; Intracranial Hypertension; Intracranial Pressure; Randomized Controlled Trials as Topic; Saline Solution, Hypertonic
PubMed: 31978260
DOI: 10.1002/14651858.CD010904.pub3 -
The Cochrane Database of Systematic... Dec 2019Increased intracranial pressure (ICP) has been shown to be strongly associated with poor neurological outcomes and mortality for patients with acute traumatic brain... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Increased intracranial pressure (ICP) has been shown to be strongly associated with poor neurological outcomes and mortality for patients with acute traumatic brain injury (TBI). Currently, most efforts to treat these injuries focus on controlling the ICP. Hypertonic saline (HTS) is a hyperosmolar therapy that is used in traumatic brain injury to reduce intracranial pressure. The effectiveness of HTS compared with other ICP-lowering agents in the management of acute TBI is still debated, both in the short and the long term.
OBJECTIVES
To assess the comparative efficacy and safety of hypertonic saline versus other ICP-lowering agents in the management of acute TBI.
SEARCH METHODS
We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Library, PubMed, Embase Classic+Embase (OvidSP), ISI Web of Science: Science Citation Index and Conference Proceedings Citation Index-Science, as well as trials registers, on 11 December 2019. We supplemented these searches using four major Chinese databases on 19 September 2018. We also checked bibliographies, and contacted study authors to identify additional studies.
SELECTION CRITERIA
We sought to identify all randomised controlled trials (RCTs) of HTS versus other intracranial pressure-lowering agents for people with acute TBI of any severity. We excluded cross-over trials as incompatible with assessing long term outcomes.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened search results to identify potentially eligible trials and extracted data using a standard data extraction form. Outcome measures included: mortality at end of follow-up (all-cause); death or disability (as measured by the Glasgow Outcome Scale (GOS)); uncontrolled ICP (defined as failure to decrease the ICP to target and/or requiring additional intervention); and adverse events (AEs) (e.g. rebound phenomena; pulmonary oedema; acute renal failure during treatment).
MAIN RESULTS
Six trials, involving data from 295 people, met the inclusion criteria. The majority of participants (89%) had a diagnosis of severe TBI. We had concerns about particular domains of risk of bias in each trial, as physicians were not reliably blinded to allocation, two trials contained participants with conditions other than TBI and in one trial, there were concerns about missing data for important outcomes. The original protocol was available for only one study and other trials (where registered) were registered retrospectively. Meta-analysis for both the primary outcome (mortality at final follow up) and for 'poor outcome' as per conventionally dichotomised GOS criteria, was only possible for two studies. Synthesis of long-term outcomes was inhibited by the fact that two ceased data collection within two hours of a single bolus dose of an ICP-lowering agent and one at discharge from ICU. Only three studies collected data after release from hospital. Due to variation in modes of drug administration, follow-up times, and ways of reporting changes in ICP, as well as no uniform definition of 'uncontrolled ICP', we did not perform meta-analysis for this outcome and report results narratively, by individual trial. Trials tended to report both treatments to be effective in reducing elevated ICP but that HTS had increased benefits, usually adding that pretreatment factors need to be considered (e.g. serum sodium and both system and brain hemodynamics). No trial provided data for our other outcomes of interest. Evidence for all outcomes is considered very low, as assessed by GRADE. All conclusions were downgraded due to imprecision (small sample size), indirectness (due to choice of measurement and/or selection of patients without TBI), and in some cases, risk of bias and inconsistency. Only one of the included trials reported data on adverse effects (AEs) - a rebound phenomenon, which was present only in the comparator group (mannitol). No data were reported on pulmonary oedema or acute renal failure during treatment. On the whole, investigators do not seem to have rigorously sought to collect data on AEs.
AUTHORS' CONCLUSIONS
This review set out to find trials comparing HTS to a potential range of other ICP-lowering agents, but only identified trials comparing it with mannitol or mannitol in combination with glycerol. Based on limited data, there is weak evidence to suggest that HTS is no better than mannitol in efficacy and safety in the long-term management of acute TBI. Future research should be comprised of large, multi-site trials, prospectively registered, reported in accordance with current best practice. Issues such as the type of TBI suffered by participants and concentration of infusion and length of time over which the infusion is given should be investigated.
Topics: Brain Injuries; Brain Injuries, Traumatic; Glasgow Outcome Scale; Humans; Intracranial Hypertension; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Saline Solution, Hypertonic
PubMed: 31886900
DOI: 10.1002/14651858.CD010904.pub2