In this study, we present data on the use of subcutaneous (SC) rapid-acting insulin aspart in the treatment of children and adolescents with mild and moderate DKA in a large referral public hospital. Our results indicated that subcutaneous injection of insulin aspart every two hours which removed the need for ICU admission was found to be an effective, safe, and convenient alternative for the treatment of mild to moderate DKA in pediatric patients. This finding confirms the results of previous studies regarding the safety, cost-effectiveness, and feasibility of subcutaneous insulin administration which similarly removed the need for intensive care unit admission without causing any mortality or serious adverse effects in the management of patients with mild to moderate DKA. The results of previous studies suggest that subcutaneous insulin also reduces the discomfort of patients [17, 24, 25, 27]. In this regard Ersöz et al demonstrated that the treatment of mild and moderate DKA with SC insulin lispro is equally effective and safe compared with regular IV insulin [28]. Similarly, Vincent et al stated that treatment of mild and moderate DKA with subcutaneous insulin lispro is a practical alternative protocol to conventional IV infusion of regular insulin [27]. Castellanos et al reviewed and compared the results of five randomized controlled trials conducted primarily in adults on effects of SC insulin analogs versus regular IV insulin for treatment of diabetic ketoacidosis. They found that there were no significant advantages or disadvantages between the two treatment protocols [29].
During the Covid-19 pandemic, critical care resources were limited and there was a fear of the risk of transmission of Covid-19 infection to the hospitalized young people with type 1 or type 2 diabetes. Based on considerable evidence on the safety and efficacy of subcutaneous insulin therapy in the treatment of mild and moderate ketoacidosis [17, 24, 25, 27, 28, 30, 31], the International Society for Pediatric and Adolescent Diabetes (ISPAD) in a scientific guideline recommended that in some critical situations, such as the Covid-19 pandemic, subcutaneous insulin therapy is a valid alternative to intravenous insulin in patients with non-severe diabetic ketoacidosis. This guideline notes that the mentioned strategy allows these patients to be admitted to medical wards far away from the patients with Covid-19 in order to reduce the risk of transmission of infection and to provide more ICU beds for patients with Covid-19 [23].
We observed that the time taken to the resolution of ketoacidosis and clinical improvement (11.24 ± 5.8 hours) was similar to a previously published report from our center [30]. As expected, the duration of treatment was longer in the moderate group compared to the mild group (13.67 hours versus 9 hours). Bali et al compared SC versus IV treatments in DKA resolution (9.01 h in SC group vs 11.9 h in intravenous group [31].
In agreement with recent reports by Andrade-Castellanos et al [29], our alternative treatment method was also accompanied by another benefit which was short hospital course (mean 2.3 days). In a previous study in our center, we found that the length of hospitalization in patients treated with subcutaneous insulin was less than those treated with intravenous insulin (3.38 days versus 4.42 days) [30]. However, some previous authors did not find a significant change in the length of hospitalization in patients treated with subcutaneous insulin [2, 14, 21, 31]. In the study conducted by Umpierrez et al, no difference was observed in the duration of hospitalization, but the cost of admission was lower in the group treated with subcutaneous insulin [14]. The explanation for why the length of stay of our patients in the hospital was less than similar studies may be that 64% of the participants in this research were patients known to have T1DM and so were discharged earlier than the patients who were new case of T1DM that needed to receive basic training for living with diabetes.
In coherence with the results from previous studies [2, 28, 30], in the present work, none of the patients exhibited biochemical and clinical signs suggestive of hypoglycemia, hypokalemia, and hyponatremia which is one of the important advantages of this alternative method [2, 28, 30]. While by using intravenous insulin, significant hypoglycemia and hypokalemia continue to be areas of concern [32].
There were no cases of acute kidney failure or renal tubular necrosis which are one of the complications of diabetic ketoacidosis [33]. No other adverse effects were found in association with SC insulin aspart. One case with moderate DKA was non-response during the SC treatment with insulin aspart and was transferred to pediatric ICU and treated with intravenous insulin protocol.
Another notable observation was that the majority of patients and parents felt satisfied that they were not admitted to the pediatric intensive care unit (PICU). PICU admission exposes children and their families to a wide range of stressful experiences with long-term psychological consequences, cognitive impairment, emotional and behavioral problems because of what happens to the patient themselves and also, the events that they witness for other patients in the special care department [34–38]. Subcutaneous insulin therapy, which does not require ICU admission, may effectively minimize, or prevent the long-term psychological effects of ICU admission.
Finally, avoiding ICU admission of patients with uncomplicated DKA would make more ICU beds available for patients with more complex conditions, reducing healthcare costs and improving resource utilization.
Despite all the advantages mentioned above, it can be argued that the current protocol was performed on the carefully selected patients under the supervision of trained personnel and experienced medical team familiar with the treatment of children and adolescents with diabetic ketoacidosis in the endocrinology department where rapid return of laboratory test results was possible. The implementation of this treatment method in medical centers without favorable facilities may lead to the deterioration of the clinical condition of patients. This creates the first limitation of this study, and additional prospective studies are required to assess the generalizability, benefits, and disadvantages of SC versus standard protocol of slow IV insulin infusion therapy in management of DKA. Secondly, repeated injections of insulin every two hours can be painful and inconvenient for a child. Nevertheless, our study’s results corroborate and strengthen the knowledge of treating patients with mild and moderate ketoacidosis with subcutaneous insulin.