Evidence
This page contains a snapshot of featured content which highlights evidence addressing key clinical questions including areas of uncertainty. Please see the main topic reference list for details of all sources underpinning this topic.
BMJ Best Practice evidence tables
Evidence tables provide easily navigated layers of evidence in the context of specific clinical questions, using GRADE and a BMJ Best Practice Effectiveness rating. Follow the links at the bottom of the table, which go to the related evidence score in the main topic text, providing additional context for the clinical question. Find out more about our evidence tables.
This table is a summary of the analysis reported in a systematic review that focuses on the above important clinical question.
Confidence in the evidence is very low or low where GRADE has been performed and the intervention may be more effective/beneficial than the comparison for key outcomes. However this is uncertain and new evidence could change this in the future.
Population: People with DKA (critical and non-critical care settings)
Intervention: Balanced crystalloid solutions
Comparison: Normal saline
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Adults and children with DKA (8 RCTs, search date March 2021) | ||
Mortality | No statistically significant difference | Very Low |
DKA resolution | No statistically significant difference | Moderate |
Time to DKA resolution (hours) | Favors intervention | Moderate |
Duration of hospital stay (days) | Favors intervention | Moderate |
Post-resuscitation bicarbonate levels (mmol/L) | Favors intervention | Moderate |
Post-resuscitation chloride levels (mmol/L) | No statistically significant difference | Low |
Adults with DKA (7 RCTs and 3 observational studies, search date November 2021) | ||
Mortality | No statistically significant difference | GRADE not assessed for this outcome |
Time to DKA resolution (hours) | Favors intervention | Low |
Duration of parenteral insulin administration (hours) ᵃ | No statistically significant difference | Low |
Amount of total fluid administration (mL) ᵇ | No statistically significant difference | Low |
Post-resuscitation potassium levels (mmol/L) | No statistically significant difference | Very Low |
Post-resuscitation chloride levels (mmol/L) | Favors intervention | Very Low |
Post-resuscitation bicarbonate levels (mmol/L) | Favors intervention | Moderate |
Post-resuscitation sodium levels (mmol/L) | Favors intervention | Low |
Note The authors of both systematic reviews concluded that as supporting evidence remains weak, further studies are still needed. The authors of the systematic review in adults and children highlighted the following limitations: included RCTs were generally small resulting in important issues with imprecision; heterogeneity in some outcomes (e.g., time to DKA resolution) possibly due to variability in definition between included studies. The authors of the systematic review in adults only highlighted the following limitations: studies using different criteria to define DKA recovery (e.g., varying blood chemistry cutoffs) and evaluating patients with different ages and severity levels; different types of balanced fluids were used across the included studies; patient groups varied across included studies (some studies included critically ill patients while others did not). ᵃ Results based on observational evidence; the forest plot also includes RCT evidence which reports no statistically significant difference between treatment groups; no GRADE reported. ᵇ The systematic review reported RCT and observational data meta-analyses separately for this outcome; both sets of results found no statistically significant difference between treatment groups and GRADE assessed as Low. For more information on systematic review in adults and children see full text at: https://journals.lww.com/ccejournal/fulltext/10.1097/cce.0000000000000613~saline-compared-to-balanced-crystalloid-in-patients-with For more information on systematic review in adults only see full text at: https://onlinelibrary.wiley.com/doi/10.1002/dmrr.3831
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a Cochrane Clinical Answer that focuses on the above important clinical question.
Confidence in the evidence is very low or low where GRADE has been performed and there may be no difference in effectiveness between the intervention and comparison for key outcomes. However this is uncertain and new evidence could change this in the future.
Population: People with type 1 or 2 diabetes with DKA
Intervention: Rapid‐acting insulin analog administered subcutaneously
Comparison: Regular short-acting insulin administered intravenously
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Time to resolution of diabetic ketoacidosis | No statistically significant difference | Very Low |
All‐cause mortality | See note ᵃ | Moderate |
Hypoglycemic episodes | No statistically significant difference | Low |
Duration of hospital stay | No statistically significant difference | Low |
Adverse events other than hypoglycemia | - | None of the studies identified by the review reported this outcome |
Note Four trials evaluated insulin lispro and one evaluated insulin aspart. While the results in the table above reflect the insulin lispro data, findings for insulin aspart were identical, with the exception of all-cause mortality, which received a low GRADE rating. The Cochrane review which underpins this Cochrane Clinical Answer (CCA) noted that the criteria for DKA used in the included trials were consistent with the American Diabetes Association criteria for mild or moderate DKA. Most trials did not report the underlying type of diabetes. Where reported, the most common precipitating causes of DKA were poor compliance with diabetes therapy (54%), infection (31%) and new-onset diabetes (15%). Three trials excluded people with acute myocardial ischaemia, end‐stage kidney disease, anasarca, and pregnancy. Other exclusion criteria used were dementia, heart failure, recent surgery, corticosteroid or immunosuppressant use, and liver failure. ᵃ No deaths were reported in either group; the CCA noted that no trial was adequately powered for this outcome.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review) that focuses on the above important clinical question.
Confidence in the evidence is very low or low where GRADE has been performed and there may be no difference in effectiveness between the intervention and comparison for key outcomes. However this is uncertain and new evidence could change this in the future.
Population: Adults with sepsis-induced hypotension
Intervention: Immediate vasopressor therapy
Comparison: Delayed vasopressor therapy
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Mortality | Favors intervention | Low |
Renal Replacement Therapy (RRT) | No statistically significant difference | Low |
Mechanical Ventilation | No statistically significant difference | Low |
Ventilator free days | No statistically significant difference | Low |
RRT free days | No statistically significant difference | Low |
Organ support free days | No statistically significant difference | Very Low |
Adverse events - Pulmonary Edema | Occurs more commonly with delayed vasopressor compared with immediate vasopressor (favours intervention) | Very Low |
Adverse events - Arrhythmia | Occurs more commonly with delayed vasopressor compared with immediate vasopressor (favours intervention) | Low |
Adverse events - (Upper gastrointestinal bleeding [UGIB]; Limb or intestinal ischemia; Skin Necrosis; Acute Respiratory Distress Syndrome [ARDS]) | No statistically significant difference | Very Low |
Vasopressors free days | Favors intervention | Low |
Fluids ml/kg | Favors intervention | Very Low |
Recommendations as stated in the source guideline For adults with sepsis-induced hypotension, we “suggest” initial intravenous crystalloid fluid bolus resuscitation followed by vasopressor support if hypotension persists (conditional recommendation, very low certainty evidence)
Note The guideline developers noted that many studies excluded patients with severe comorbidity or who were in a critical condition. They discussed the importance of considering the risk-benefit ratio for different patient groups; with early therapy more likely to be overall beneficial for people with life-threatening end-organ hypoperfusion, whereas patients responsive to fluid bolus resuscitation are more at risk from the potential harms of unnecessary catecholamine exposure. They added a remark to their recommendation stating that for patients with unstable shock it may be appropriate to give immediate concurrent vasopressor and intravenous fluid therapy on a case-by-case basis. They also noted that one RCT compared restrictive fluids with early vasopressors versus liberal fluids and later vasopressors that found no significant difference for the following outcomes: Mortality hospital at 90 days; Organ support free days; Ventilator free days 28 days; RRT free days 28 days; Vasopressors free days; Invasive ventilation; RRT. The guideline developers agreed that further large RCTs are needed to confirm optimal timing of vasopressor therapy.
This evidence table is related to the following section/s:
Cochrane Clinical Answers
Cochrane Clinical Answers (CCAs) provide a readable, digestible, clinically focused entry point to rigorous research from Cochrane systematic reviews. They are designed to be actionable and to inform decision making at the point of care and have been added to relevant sections of the main Best Practice text.
- How do subcutaneous rapid-acting insulin analogs compare with regular insulin in people with diabetic ketoacidosis?
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