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Lancet (London, England) Nov 2022Large trials have shown that sodium glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of adverse kidney and cardiovascular outcomes in patients with heart... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Large trials have shown that sodium glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of adverse kidney and cardiovascular outcomes in patients with heart failure or chronic kidney disease, or with type 2 diabetes and high risk of atherosclerotic cardiovascular disease. None of the trials recruiting patients with and without diabetes were designed to assess outcomes separately in patients without diabetes.
METHODS
We did a systematic review and meta-analysis of SGLT2 inhibitor trials. We searched the MEDLINE and Embase databases for trials published from database inception to Sept 5, 2022. SGLT2 inhibitor trials that were double-blind, placebo-controlled, performed in adults (age ≥18 years), large (≥500 participants per group), and at least 6 months in duration were included. Summary-level data used for analysis were extracted from published reports or provided by trial investigators, and inverse-variance-weighted meta-analyses were conducted to estimate treatment effects. The main efficacy outcomes were kidney disease progression (standardised to a definition of a sustained ≥50% decrease in estimated glomerular filtration rate [eGFR] from randomisation, a sustained low eGFR, end-stage kidney disease, or death from kidney failure), acute kidney injury, and a composite of cardiovascular death or hospitalisation for heart failure. Other outcomes were death from cardiovascular and non-cardiovascular disease considered separately, and the main safety outcomes were ketoacidosis and lower limb amputation. This study is registered with PROSPERO, CRD42022351618.
FINDINGS
We identified 13 trials involving 90 413 participants. After exclusion of four participants with uncertain diabetes status, we analysed 90 409 participants (74 804 [82·7%] participants with diabetes [>99% with type 2 diabetes] and 15 605 [17·3%] without diabetes; trial-level mean baseline eGFR range 37-85 mL/min per 1·73 m). Compared with placebo, allocation to an SGLT2 inhibitor reduced the risk of kidney disease progression by 37% (relative risk [RR] 0·63, 95% CI 0·58-0·69) with similar RRs in patients with and without diabetes. In the four chronic kidney disease trials, RRs were similar irrespective of primary kidney diagnosis. SGLT2 inhibitors reduced the risk of acute kidney injury by 23% (0·77, 0·70-0·84) and the risk of cardiovascular death or hospitalisation for heart failure by 23% (0·77, 0·74-0·81), again with similar effects in those with and without diabetes. SGLT2 inhibitors also reduced the risk of cardiovascular death (0·86, 0·81-0·92) but did not significantly reduce the risk of non-cardiovascular death (0·94, 0·88-1·02). For these mortality outcomes, RRs were similar in patients with and without diabetes. For all outcomes, results were broadly similar irrespective of trial mean baseline eGFR. Based on estimates of absolute effects, the absolute benefits of SGLT2 inhibition outweighed any serious hazards of ketoacidosis or amputation.
INTERPRETATION
In addition to the established cardiovascular benefits of SGLT2 inhibitors, the randomised data support their use for modifying risk of kidney disease progression and acute kidney injury, not only in patients with type 2 diabetes at high cardiovascular risk, but also in patients with chronic kidney disease or heart failure irrespective of diabetes status, primary kidney disease, or kidney function.
FUNDING
UK Medical Research Council and Kidney Research UK.
Topics: Humans; Adult; Adolescent; Sodium-Glucose Transporter 2 Inhibitors; Diabetes Mellitus, Type 2; Sodium-Glucose Transporter 2; Kidney; Acute Kidney Injury; Renal Insufficiency, Chronic; Heart Failure; Ketosis; Disease Progression; Glucose; Sodium; Randomized Controlled Trials as Topic
PubMed: 36351458
DOI: 10.1016/S0140-6736(22)02074-8 -
Kidney & Blood Pressure Research 2020The etiology of acute metabolic acidosis (aMA) is heterogeneous, and the consequences are potentially life-threatening. The aim of this article was to summarize the...
BACKGROUND
The etiology of acute metabolic acidosis (aMA) is heterogeneous, and the consequences are potentially life-threatening. The aim of this article was to summarize the causes and management of aMA from a clinician's perspective.
SUMMARY
We performed a systematic search on PubMed, applying the following search terms: "acute metabolic acidosis," "lactic acidosis," "metformin" AND "acidosis," "unbalanced solutions" AND "acidosis," "bicarbonate" AND "acidosis" AND "outcome," "acute metabolic acidosis" AND "management," and "acute metabolic acidosis" AND "renal replacement therapy (RRT)/dialysis." The literature search did not consider diabetic ketoacidosis at all. Lactic acidosis evolves from various conditions, either with or without systemic hypoxia. The incidence of metformin-associated aMA is actually quite low. Unbalanced electrolyte preparations can induce hyperchloremic aMA. The latter potentially worsens kidney-related outcome parameters. Nevertheless, prospective and controlled data are missing at the moment. Recently, bicarbonate has been shown to improve clinically relevant endpoints in the critically ill, even if higher pH values (>7.3) are targeted. New therapeutics for aMA control are under development, since bicarbonate treatment can induce serious side effects. Key Messages: aMA is a frequent and potentially life-threatening complication of various conditions. Lactic acidosis might occur even in the absence of systemic hypoxia. The incidence of metformin-associated aMA is comparably low. Unbalanced electrolyte solutions induce hyperchloremic aMA, which most likely worsens the renal prognosis of critically ill patients. Bicarbonate, although potentially deleterious due to increased carbon dioxide production with subsequent intracellular acidosis, improves kidney-related endpoints in the critically ill.
Topics: Acidosis; Acidosis, Lactic; Acute Disease; Animals; Bicarbonates; Disease Management; Electrolytes; Humans; Hypoglycemic Agents; Metformin
PubMed: 32663831
DOI: 10.1159/000507813 -
Current Gastroenterology Reports Jun 2017This study aimed to systematically review small bowel obstruction (SBO), focusing on recent changes in diagnosis/therapy. (Review)
Review
PURPOSE OF REVIEW
This study aimed to systematically review small bowel obstruction (SBO), focusing on recent changes in diagnosis/therapy.
RECENT FINDINGS
SBO incidence is about 350,000/annum in the USA. Etiologies include adhesions (65%), hernias (10%), neoplasms (5%), Crohn's disease (5%), and other (15%). Bowel dilatation occurs proximal to obstruction primarily from swallowed air and secondarily from intraluminal fluid accumulation. Dilatation increases mural tension, decreases mucosal perfusion, causes bacterial proliferation, and decreases mural tensile strength that increases bowel perforation risks. Classical clinical tetrad is abdominal pain, nausea and emesis, abdominal distention, and constipation-to-obstipation. Physical exam may reveal restlessness, acute illness, and signs of dehydration and sepsis, including tachycardia, pyrexia, dry mucous membranes, hypotension/orthostasis, abdominal distention, and hypoactive bowel sounds. Severe direct tenderness, involuntary guarding, abdominal rigidity, and rebound tenderness suggest advanced SBO, as do marked leukocytosis, neutrophilia, bandemia, and lactic acidosis. Differential diagnosis includes postoperative ileus, narcotic bowel, colonic pseudo-obstruction, mesenteric ischemia, and large bowel obstruction. Medical resuscitation includes intravenous hydration, correcting electrolyte abnormalities, intravenous antibiotics, nil per os, and nasoenteral suction. Abdominal CT with oral and intravenous gastrografin contrast is highly sensitive and specific in detecting/characterizing SBO. SBO usually resolves with medical therapy but requires surgery, preferentially by laparoscopy, for unremitting total obstruction, bowel perforation, severe ischemia, or clinical deterioration with medical therapy. Overall mortality is 10% but increases to 30% with bowel necrosis/perforation. Key point in SBO is early diagnosis, emphasizing abdominal CT; aggressive medical therapy including rehydration, antibiotics, and nil per os; and surgery for failed medical therapy.
Topics: Abdominal Pain; Diagnosis, Differential; Dilatation, Pathologic; Humans; Ileus; Intestinal Obstruction; Intestine, Small; Laparoscopy; Nausea; Physical Examination; Postoperative Complications; Vomiting
PubMed: 28439845
DOI: 10.1007/s11894-017-0566-9 -
Current Diabetes Reports Aug 2021To assess the pleiotropic effects of ketogenic diets (KD) on glucose control, changes in medication, and weight loss in individuals with type 2 diabetes, and to evaluate... (Review)
Review
To assess the pleiotropic effects of ketogenic diets (KD) on glucose control, changes in medication, and weight loss in individuals with type 2 diabetes, and to evaluate its practical feasibility RECENT FINDINGS: KD results in improved HbA1c already after 3 weeks, and the effect seems to persist for at least 1 year. This is associated with a reduction in glucose-lowering medications. The weight loss observed after a short time period seems to be maintained with a long-term diet. Adequate support (supportive psychological counseling, enhancing positive affectivity, reinforcing mindful eating) is necessary to achieve a benefit and to assure adherence. Despite the documented decrease in HbA1, a definitive causal effect of KD remains to be proven. KD should be performed under strict medical supervision. Future research should clarify how compliance can be maximized and how ketosis can be optimally monitored.
Topics: Diabetes Mellitus, Type 2; Diet, Carbohydrate-Restricted; Diet, Ketogenic; Humans; Ketosis; Weight Loss
PubMed: 34448957
DOI: 10.1007/s11892-021-01399-z -
Journal of Medical Virology Nov 2022Viral infections may increase the risk of developing type 1 diabetes (T1D), and recent reports suggest that Coronavirus Disease 2019 (COVID-19) might have increased the... (Meta-Analysis)
Meta-Analysis Review
Viral infections may increase the risk of developing type 1 diabetes (T1D), and recent reports suggest that Coronavirus Disease 2019 (COVID-19) might have increased the incidence of pediatric T1D and/or diabetic ketoacidosis (DKA). Therefore, this meta-analysis aims to estimate the risk of global pediatric new-onset T1D, DKA, and severe DKA before and after the COVID-19 pandemic. A systematic search of MEDLINE/PubMed, CINAHL, Scopus, and EMBASE was conducted for articles published up to March 2022. A random-effects meta-analysis was performed to compare the relative risk of T1D and DKA among pediatric patients with T1D between the COVID-19 pre-pandemic and pandemic periods. We also compared glucose and HbA1c values in children who were newly diagnosed with T1D before and after the COVID-19 pandemic. The global incidence rate of T1D in the 2019 period was 19.73 per 100 000 children and 32.39 per 100 000 in the 2020 period. Compared with pre-COVID-19 pandemic, the number of worldwide pediatric new-onset T1D, DKA, and severe DKA during the first year of the COVID-19 pandemic increased by 9.5%, 25%, and 19.5%, respectively. Compared with pre-COVID-19 pandemic levels, the median glucose, and HbA1c values in newly diagnosed T1D children after the COVID-19 pandemic increased by 6.43% and 6.42%, respectively. The COVID-19 pandemic has significantly increased the risk of global pediatric new-onset T1D, DKA, and severe DKA. Moreover, higher glucose and HbA1c values in newly diagnosed T1D children after the COVID-19 pandemic mandates targeted measures to raise public and physician awareness.
Topics: COVID-19; Child; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Glucose; Glycated Hemoglobin; Humans; Incidence; Pandemics
PubMed: 35831242
DOI: 10.1002/jmv.27996 -
Pharmacotherapy Sep 2019Hyperlactatemia and lactic acidosis are two syndromes that are associated with morbidity and mortality. Medication-induced hyperlactatemia and lactic acidosis are...
Hyperlactatemia and lactic acidosis are two syndromes that are associated with morbidity and mortality. Medication-induced hyperlactatemia and lactic acidosis are diagnoses of exclusion and have the potential to be overlooked. The purposes of this systematic review are to identify published reports of medication-induced lactate level elevations to aid clinicians in diagnosing and comprehending the underlying mechanism of this rare adverse drug effect and to provide management strategies. The PubMed database was searched for case reports, case series, retrospective studies, and prospective studies describing cases of medication-induced lactate level elevation, including lactic acidosis and hyperlactatemia, published between January 1950 and June 2017. A standardized search strategy was used, and the articles identified underwent two rounds of independent evaluation by two reviewers to assess for inclusion. Articles were included if they described at least one patient older than 12 years with hyperlactatemia or lactic acidosis caused by a medication with United States Food and Drug Administration (FDA) approval and if alternative etiologies for an elevated lactate level were ruled out. Metformin and nucleoside/nucleotide reverse transcriptase inhibitors were excluded since the pathophysiology and incidence of lactic acidosis have been well established for these agents. Overall, 1918 articles were identified, and 101 met inclusion criteria. A total of 286 patients experienced medication-induced lactate level elevations, from which 59 unique medications were identified. The most commonly identified agents were epinephrine and albuterol. Medication-induced lactate level elevation was classified as lactic acidosis (64.0%), hyperlactatemia (31.1%), or not specified (4.9%). The doses ingested included FDA-labeled doses (86%), intentional overdoses (10.8%), or prescribed doses exceeding the FDA-labeled dose (3.1%). Medications were continued without a change (40.8%), were permanently discontinued (34.4%), were continued with a dosage reduction (11.6%), or were initially withheld then resumed after lactate level normalized (2.9%); medication management for the remaining 10.0% was not reported. Forty-six patients died (16%). Six deaths were attributed by treating clinicians to be secondary to medication-induced lactic acidosis. Management strategies were heterogeneous, and treatment included supportive care, exogenous bicarbonate therapy, medication specific antidotes, and decontamination strategies. Unexplained lactate level elevations should prompt clinicians to assess for medication-induced lactate level elevations. Pharmacists are members of the health care team that are well positioned to serve as experts in the diagnosis and management of medication-induced lactate level elevations.
Topics: Acidosis, Lactic; Dose-Response Relationship, Drug; Drug Overdose; Humans; Hyperlactatemia; Prescription Drug Misuse; Prescription Drugs; United States
PubMed: 31361914
DOI: 10.1002/phar.2316 -
Pharmacotherapy Feb 2017Currently only minimal information is available regarding risk factors for the development of sodium glucose cotransporter-2 inhibitor (SGLT2i)-related diabetic... (Review)
Review
STUDY OBJECTIVE
Currently only minimal information is available regarding risk factors for the development of sodium glucose cotransporter-2 inhibitor (SGLT2i)-related diabetic ketoacidosis (DKA). We aim to identify individual patient characteristics associated with cases of SGLT2i-related DKA to better describe potential risk factors.
DESIGN
Systematic review of primary literature.
PATIENTS
Thirty-four case reports of patients with type 1 and type 2 diabetes mellitus who developed DKA while receiving an SGLT2i.
METHODS AND MAIN RESULTS
This systematic review investigated the relationship between SGLT2i and DKA in patients with diabetes. The existing literature was reviewed with a primary outcome to identify patient-specific factors contributing to the incidence of ketoacidosis in patients with diabetes who were treated with a SGLT2i. Numerous databases were searched to identify appropriate primary literature. Search terms included canagliflozin, dapagliflozin, empagliflozin, SGLT2, sodium glucose cotransporter-2 inhibitor, diabetic ketoacidosis, ketoacidosis, metabolic acidosis, and acidosis. Primary literature was analyzed via descriptive statistics. Thirty-four individual case reports were identified via the primary literature search. Two-thirds (25 cases) involved patients with a diagnosis of type 2 diabetes mellitus (T2DM). The average blood glucose on presentation for SGLT2i-induced DKA was 265.6 ± 140.7 mg/dl (14.7 ± 7.8 mmol/L), with common symptoms including nausea, vomiting, and abdominal pain. Common precipitating factors included patients who were diagnosed with T2DM and were subsequently found to have latent autoimmune diabetes of adulthood, patients who had recently undergone major surgery, or patients who had decreased or discontinued insulin. No cases were fatal.
CONCLUSION
In this review, episodes of DKA with SGLT2i use were characterized by lower blood glucose levels and were often caused by a precipitating factor. Understanding precipitating factors for SGLT2i-related DKA may help providers better identify patients at risk for development of DKA.
Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Female; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Risk Factors; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 27931088
DOI: 10.1002/phar.1881 -
JAMAMetformin is widely viewed as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus. However, the drug is... (Review)
Review
IMPORTANCE
Metformin is widely viewed as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus. However, the drug is contraindicated in many individuals with impaired kidney function because of concerns of lactic acidosis.
OBJECTIVE
To assess the risk of lactic acidosis associated with metformin use in individuals with impaired kidney function.
EVIDENCE ACQUISITION
In July 2014, we searched the MEDLINE and Cochrane databases for English-language articles pertaining to metformin, kidney disease, and lactic acidosis in humans between 1950 and June 2014. We excluded reviews, letters, editorials, case reports, small case series, and manuscripts that did not directly pertain to the topic area or that met other exclusion criteria. Of an original 818 articles, 65 were included in this review, including pharmacokinetic/metabolic studies, large case series, retrospective studies, meta-analyses, and a clinical trial.
RESULTS
Although metformin is renally cleared, drug levels generally remain within the therapeutic range and lactate concentrations are not substantially increased when used in patients with mild to moderate chronic kidney disease (estimated glomerular filtration rates, 30-60 mL/min per 1.73 m2). The overall incidence of lactic acidosis in metformin users varies across studies from approximately 3 per 100,000 person-years to 10 per 100,000 person-years and is generally indistinguishable from the background rate in the overall population with diabetes. Data suggesting an increased risk of lactic acidosis in metformin-treated patients with chronic kidney disease are limited, and no randomized controlled trials have been conducted to test the safety of metformin in patients with significantly impaired kidney function. Population-based studies demonstrate that metformin may be prescribed counter to prevailing guidelines suggesting a renal risk in up to 1 in 4 patients with type 2 diabetes mellitus--use which, in most reports, has not been associated with increased rates of lactic acidosis. Observational studies suggest a potential benefit from metformin on macrovascular outcomes, even in patients with prevalent renal contraindications for its use.
CONCLUSIONS AND RELEVANCE
Available evidence supports cautious expansion of metformin use in patients with mild to moderate chronic kidney disease, as defined by estimated glomerular filtration rate, with appropriate dosage reductions and careful follow-up of kidney function.
Topics: Acidosis, Lactic; Contraindications; Diabetes Mellitus, Type 2; Glomerular Filtration Rate; Humans; Hypoglycemic Agents; Metformin; Renal Insufficiency, Chronic; Risk
PubMed: 25536258
DOI: 10.1001/jama.2014.15298 -
American Journal of Physiology. Renal... Dec 2016Insulin resistance (IR) is an early metabolic alteration in chronic kidney disease (CKD) patients, being apparent when the glomerular filtration rate is still within the... (Review)
Review
Insulin resistance (IR) is an early metabolic alteration in chronic kidney disease (CKD) patients, being apparent when the glomerular filtration rate is still within the normal range and becoming almost universal in those who reach the end stage of kidney failure. The skeletal muscle represents the primary site of IR in CKD, and alterations at sites beyond the insulin receptor are recognized as the main defect underlying IR in this condition. Estimates of IR based on fasting insulin concentration are easier and faster but may not be adequate in patients with CKD because renal insufficiency reduces insulin catabolism. The hyperinsulinemic euglycemic clamp is the gold standard for the assessment of insulin sensitivity because this technique allows a direct measure of skeletal muscle sensitivity to insulin. The etiology of IR in CKD is multifactorial in nature and may be secondary to disturbances that are prominent in renal diseases, including physical inactivity, chronic inflammation, oxidative stress, vitamin D deficiency, metabolic acidosis, anemia, adipokine derangement, and altered gut microbiome. IR contributes to the progression of renal disease by worsening renal hemodynamics by various mechanisms, including activation of the sympathetic nervous system, sodium retention, and downregulation of the natriuretic peptide system. IR has been solidly associated with intermediate mechanisms leading to cardiovascular (CV) disease in CKD including left ventricular hypertrophy, vascular dysfunction, and atherosclerosis. However, it remains unclear whether IR is an independent predictor of mortality and CV complications in CKD. Because IR is a modifiable risk factor and its reduction may lower CV morbidity and mortality, unveiling the molecular mechanisms responsible for the pathogenesis of CKD-related insulin resistance is of importance for the identification of novel therapeutic targets aimed at reducing the high CV risk of this condition.
Topics: Disease Progression; Glucose Clamp Technique; Humans; Inflammation; Insulin Resistance; Oxidative Stress; Renal Insufficiency, Chronic; Vitamin D Deficiency
PubMed: 27707707
DOI: 10.1152/ajprenal.00340.2016 -
The Cochrane Database of Systematic... Jul 2017Non-invasive ventilation (NIV) with bi-level positive airway pressure (BiPAP) is commonly used to treat patients admitted to hospital with acute hypercapnic respiratory... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Non-invasive ventilation (NIV) with bi-level positive airway pressure (BiPAP) is commonly used to treat patients admitted to hospital with acute hypercapnic respiratory failure (AHRF) secondary to an acute exacerbation of chronic obstructive pulmonary disease (AECOPD).
OBJECTIVES
To compare the efficacy of NIV applied in conjunction with usual care versus usual care involving no mechanical ventilation alone in adults with AHRF due to AECOPD. The aim of this review is to update the evidence base with the goals of supporting clinical practice and providing recommendations for future evaluation and research.
SEARCH METHODS
We identified trials from the Cochrane Airways Group Specialised Register of trials (CAGR), which is derived from systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Allied and Complementary Medicine Database (AMED), and PsycINFO, and through handsearching of respiratory journals and meeting abstracts. This update to the original review incorporates the results of database searches up to January 2017.
SELECTION CRITERIA
All randomised controlled trials that compared usual care plus NIV (BiPAP) versus usual care alone in an acute hospital setting for patients with AECOPD due to AHRF were eligible for inclusion. AHRF was defined by a mean admission pH < 7.35 and mean partial pressure of carbon dioxide (PaCO) > 45 mmHg (6 kPa). Primary review outcomes were mortality during hospital admission and need for endotracheal intubation. Secondary outcomes included hospital length of stay, treatment intolerance, complications, changes in symptoms, and changes in arterial blood gases.
DATA COLLECTION AND ANALYSIS
Two review authors independently applied the selection criteria to determine study eligibility, performed data extraction, and determined risk of bias in accordance with Cochrane guidelines. Review authors undertook meta-analysis for data that were both clinically and statistically homogenous, and analysed data as both one overall pooled sample and according to two predefined subgroups related to exacerbation severity (admission pH between 7.35 and 7.30 vs below 7.30) and NIV treatment setting (intensive care unit-based vs ward-based). We reported results for mortality, need for endotracheal intubation, and hospital length of stay in a 'Summary of findings' table and rated their quality in accordance with GRADE criteria.
MAIN RESULTS
We included in the review 17 randomised controlled trials involving 1264 participants. Available data indicate that mean age at recruitment was 66.8 years (range 57.7 to 70.5 years) and that most participants (65%) were male. Most studies (12/17) were at risk of performance bias, and for most (14/17), the risk of detection bias was uncertain. These risks may have affected subjective patient-reported outcome measures (e.g. dyspnoea) and secondary review outcomes, respectively.Use of NIV decreased the risk of mortality by 46% (risk ratio (RR) 0.54, 95% confidence interval (CI) 0.38 to 0.76; N = 12 studies; number needed to treat for an additional beneficial outcome (NNTB) 12, 95% CI 9 to 23) and decreased the risk of needing endotracheal intubation by 65% (RR 0.36, 95% CI 0.28 to 0.46; N = 17 studies; NNTB 5, 95% CI 5 to 6). We graded both outcomes as 'moderate' quality owing to uncertainty regarding risk of bias for several studies. Inspection of the funnel plot related to need for endotracheal intubation raised the possibility of some publication bias pertaining to this outcome. NIV use was also associated with reduced length of hospital stay (mean difference (MD) -3.39 days, 95% CI -5.93 to -0.85; N = 10 studies), reduced incidence of complications (unrelated to NIV) (RR 0.26, 95% CI 0.13 to 0.53; N = 2 studies), and improvement in pH (MD 0.05, 95% CI 0.02 to 0.07; N = 8 studies) and in partial pressure of oxygen (PaO) (MD 7.47 mmHg, 95% CI 0.78 to 14.16 mmHg; N = 8 studies) at one hour. A trend towards improvement in PaCO was observed, but this finding was not statistically significant (MD -4.62 mmHg, 95% CI -11.05 to 1.80 mmHg; N = 8 studies). Post hoc analysis revealed that this lack of benefit was due to the fact that data from two studies at high risk of bias showed baseline imbalance for this outcome (worse in the NIV group than in the usual care group). Sensitivity analysis revealed that exclusion of these two studies resulted in a statistically significant positive effect of NIV on PaCO. Treatment intolerance was significantly greater in the NIV group than in the usual care group (risk difference (RD) 0.11, 95% CI 0.04 to 0.17; N = 6 studies). Results of analysis showed a non-significant trend towards reduction in dyspnoea with NIV compared with usual care (standardised mean difference (SMD) -0.16, 95% CI -0.34 to 0.02; N = 4 studies). Subgroup analyses revealed no significant between-group differences.
AUTHORS' CONCLUSIONS
Data from good quality randomised controlled trials show that NIV is beneficial as a first-line intervention in conjunction with usual care for reducing the likelihood of mortality and endotracheal intubation in patients admitted with acute hypercapnic respiratory failure secondary to an acute exacerbation of chronic obstructive pulmonary disease (COPD). The magnitude of benefit for these outcomes appears similar for patients with acidosis of a mild (pH 7.30 to 7.35) versus a more severe nature (pH < 7.30), and when NIV is applied within the intensive care unit (ICU) or ward setting.
Topics: Adult; Disease Progression; Humans; Noninvasive Ventilation; Positive-Pressure Respiration; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Respiratory Insufficiency
PubMed: 28702957
DOI: 10.1002/14651858.CD004104.pub4