Diabetic ketoacidosis (CAD) is an acute and potentially mortal complication of unrelated diabetes that occurs mainly in individuals with autoimmune type 1 diabetes, but it is not rare in some patients with type 2 diabetes.traditionally performs through the administration of intravenous regular insulin infusion that begins in the emergency department and continues in the intensive care unit or an environment of high dependence unit.It is not clear if patients with CAD should be treated with other forms of treatment such as subcutaneous rapid insulin anologists.

Goals

Evaluate the effects of subcutaneous fast -acting insulin anologists for the treatment of diabetic ketoacidosis.

Search strategy

Eligible trials were identified by means of searches in Medline, Pubmed, Embase, Lilacs, Cinahl and in the Library Cochrane.Searches were searches in the sho ichtrp search portal and clinicaltcials.gov tests.The date of the last search for all databases was October 27, 2015. The references of the random controlled tests (ECA) and systematic reviews included and contact with the authors of the trials were also examined.

Selection criteria

The trials were included if they were ECA to compare the subcutaneous fast -acting insulin anologists versus standard intravenous infusion in participants with CAD of any age or sex with type 1 or type 2 diabetes and in pregnant patients.

Obtaining and analysis of data

Two authors of the review independently extracted the data, evaluated the risk of bias of the studies and their general quality through the Grade instrument.The statistical heterogeneity of the studies included was evaluated by the visual inspection of the forest diagrams and diversity was quantified by means of statistics i².The data were synthesized by meta -analysis with the random effects model or descriptive analysis, as appropriate.

Main results

Five essays randomly assigned participants (110 participants to subcutaneous rapid insulin anologists and 91 to regular intravenous insulin).The criteria for the CAD were consistent with the criteria of the American Diabetes Association for mild or moderate CAD.The underlying cause of CAD was mainly the poor compliance with the treatment of diabetes.

Most trials did not report the type of diabetes.Participants with younger diabetes and children were underrepresented in the trials included (an essay only).Four essays evaluated the effects of the Action of Action Lispro insulin, and one the effects of the fast -acting insulin analogue aspart.The average monitoring period measured according to the average hospital stay varied between two and seven days.In general, the risk of bias of the evaluated trials was uncertain in many domains and high for the realization bias for the measure of time time until the resolution of the CAD.

No deaths were reported in the trials included (186 participants; three essays; moderate quality tests [Insulina Lispro] at low [insulin aspart]).There were very low quality tests to evaluate the effects of the subcutaneous lispro insulin versus intravenous regular insulin over time until CAD resolution: DM DM (DM) 0.2 hours;95%CI: -1.7 to 2.1;P = 0.81;90 participants;Two essays.

In an essay that included children with CAD, the time to reach a glucose level of 250 mg/dl was similar between Lispro insulin and intravenous regular insulin.There were very low quality tests to evaluate the effects of theSubcutaneous aspart insulin versus intravenous regular insulin over time until CAD resolution: DM -1 hour (95%CI: -3.2 to 1.2);P = 0.36;30 participants;An essay.

There were low quality tests to evaluate the effects of subcutaneous fast -acting insulin anologists versus intravenous regular insulin on hypoglycemia episodes: six of 80 participants treated with LISPRO insulin compared to nine of 76 participants treated with regular insulin reported events reported eventshypoglycemic;Risk quotient (CR) 0.59 (95%CI: 0.23 to 1.52);P = 0.28;156 participants;Four essays.

For aspart insulin compared to regular insulin, CR for hypoglycemia episodes was 1.00 (95%CI: 0.07 to 14.55);P = 1.0;30 participants;an essay;Low quality tests.The socioeconomic effects measured according to the average duration of the hospital stay for LISPRO insulin compared to regular insulin showed a DM of -0.4 days (95%CI: -1 to 0.2);P = 0.22;90 participants;two essays;Low quality tests and for Insulin aspart compared to regular insulin 1.1 days (95%CI: -3.3 to 1.1);P = 0.32;Low quality tests.

Data on morbidity were limited, but no specific events were reported for the comparison of Lispro insulin with regular insulin.No essay reported different adverse events from hypoglycemia episodes, and no trial investigated patient satisfaction.

Authors' conclusions

This review, which mainly provided data on adults, indicates on the basis of general quality at very low quality that there are no advantages or disadvantages when the effects of subcutaneous rapid insulin analogues are compared versus intravenous regular insulin fortreat mild or moderate CAD.

RESULTS AND DISCUSSION

Summary of the main results

This systematic review analyzed the tests of all published random controlled tests (ECA) of the subcutaneous rapid insulin analogues in the treatment of diabetic ketoacidosis (CAD).Five essays were included with a total of 201 participants in this review.

The results of this review indicate that there are no significant differences in time until the resolution of the body between the analogues of fast -acting insulin subcutaneous Lisprus or aspart and the regular intravenous insulin in adult participants.

In the only trial included that evaluated the effects of Lispro insulin on children and adolescents with CAD, the resolution of acidemia took longer compared to regular intravenous insulin;The authors attributed this slower resolution to the increase in the injections interval every four hours after the initial decrease in blood glucose to less than 250 mg/dl.

With respect to hypoglycemia and the duration of hospital stay, the results obtained with subcutaneous rapid insulin analogues and regular insulin were comparable in adults and children.No deaths occurred.Data on morbidity and socio -economic effects were limited.

None of the trials reported different adverse events of hypoglycemia, patient satisfaction or glucosylated hemoglobin A1C.

Exhaustivity and applicability of evidence

The tests analyzed in this review were carried out in four different countries, three of which could be considered low or medium income countries.In particular, the majority of the participants who represented the western region of high income were from the Afro -American ethnic group.The participants with younger diabetes and the children were underrepresented in the essay cohorts.

According to theCriteria for the inclusion of analyzed essays, the results are very relevant to adults with a mild or moderate CAD episode due to poor compliance with the treatment of diabetes.The above can reflect a poor health literacy "and the lack of understanding of treatment plans, the factors associated with socioeconomic deprivation in low or medium income countries.Regarding interventions, fast -acting insulin anologists such as Lisprus insulin and Insulin aspart are wide availability for use in daily clinical practice.

Evidence quality

The risk of bias through several domains was uncertain in most of the studies included.The above was mainly due to the fact that there was no sufficient information that allowed to evaluate the risk of low or high bias, despite attempts to establish contact with the authors of the essay.According to the Graring of Recommendations Assessment, Development and Evaluation (Grade) approach, the quality of the tests was low or very low for the most important clinically.

Therefore, the available data were too few and inconsistent to provide firm tests about the effects of subcutaneous rapid insulin analogues in patients with CAD.

Potential biases in the review process

The review was carried out according to the previously published protocol.Two authors of the review independently evaluated all the appointments identified by electronic search strategies.Similarly, two review authors carried out the evaluation of the "bias risk" and data collection.There were no conflicts of interest.

It is considered that the search for ECA has been exhaustive.However, the possibility that studies with negative results are unpublished cannot be excluded.In addition, gray literature was not systematically sought.

Agreements and disagreements with other studies or reviews

This systematic review of the subcutaneous fast -acting insulin anologists for the CAD coincides with previously published reviews, Mazer 2009 and Vincent 2013, and the current guides for the treatment of a hyperglycemic crisis in adults with diabetes;Treatment with subcutaneous rapid insulin anologists (LISPRO and ASPART) appears as an option to use intravenous regular insulin in the treatment of mild and moderate CAD (2009 Kitabchi).

Authors' conclusions

Implications for practice

The analyzes indicate that, based on quality tests mainly low to very low, there are no advantages or disadvantages when comparing the effects of subcutaneous rapid insulin analogues (Lispro insulin, insulin aspart) versus regular intravenous insulin to treatCAD.These results are very relevant to adults with a mild or moderate CAD episode due to poor compliance with diabetes treatment.

Implications for research

Due to the scarcity of High quality ECA tests that compare insulin interventions for CAD, future trials have the possibility of changing the way of treating this weakening and expensive condition.

Future ECAs must adequately inform about the random assignment method and the concealment of the allocation to the treatment.The blindness of the study participants, the study staff and the result evaluators could be made with the use of double simulation designs (Double-Dummy).The follow -up of the participants must be for longer, and the authors of the essay must fulfill the principle of intention to treat.In addition, result measures should include patient satisfaction, morbidity and effectssocioeconomic.Finally, multicenter tests are preferred to ensure external validity.

Authors

Carlos A Andrade-Castellanos1, Luis Enrique Colunga-Lozano2, Netzahualpilli Delgado-Figueroa3, Daniel to Gonzalez-Padilla4
Filiation 1 Civil Hospital of Guadalajara "Dr. Juan I. Menchaca", Department of Emergency Medicine, Salvador Quevedo and Zubieta No. 750, Guadalajara, Mexico, 44340 2 Civil Hospital of Guadalajara "Fray Antonio Mayor", Department of Critical Care Medicine, Colonel StreetCalderón #777, Guadalajara, Mexico, 44320 3 Civil Hospital of Guadalajara Dr. Juan I. Menchaca, Department of Pediatrics, Salvador Quevedo and Zubieta No. 750, Guadalajara, Mexico, 44340 4 University Hospital October 12, Department of Urology, Avenida de Córdoba, s/n, Madrid, Spain, 28041

Contact information
Carlos A Andrade-Castellanos, Civil Hospital of Guadalajara "Dr. Juan I. Menchaca", Department of Emergency Medicine, Salvador Quevedo and Zubieta No. 750, Guadalajara, Mexico, 44340 E-mail: caandrade@hcg.gob.mx