Proposed Libyan Guidelines for the Management of Inpatient Hyperglycemia with Corona Virus-19 (COVID-19) Infection ()
1. Introduction
As all the studies show that glycemic control is one of the major predictors of the mortality in corona virus-19 infections (COVID-19) [1] [2] [3], that’s why implementing an effective glycemic control guideline is extremely important [4]. It’s well known that well-controlled blood glucose (BG) levels, defined as BG between 70 and 180 mg/dL (3.9 and 10.0 mmol/L) have been associated with reduced major organ failure and all-cause mortality [5]. Many recent published guidelines and approaches for the management of blood sugar for in and out COVID-19 patients were implemented [6] [7] [8] [9] [10]. We try to choose the most reasonably applicable method of glycemic control that can easily be implemented by health care staff especially those dealing with COVID-19 in-patients in Libya. The number of confirmed cases of COVID-19 infection in Libya by June 2021 was 176.701 and the total death was 3116 [11].
2. Management of Hyperglycemia in Critically Ill Patient with COVID-19 Infection in ICU
2.1. Management of DKA in COVID-19 Infection Patients
Most of the guidelines modified the DKA management protocol to effectively treat serious hyperglycemia and in mean time reducing the risk of exposure of health staff and this especially critical as there is shortage of protective equipment and nursing staff in Libya. The corner of this modification was the use of the Subcutaneous approach rather than intravenous one in patient who are not severely acidotic (pH > 7, HCO3 > 10) and non-pregnant female. Also, the use of insulin analogue, the long acting once daily and rapid acting every 3 hours by most of the published guidelines especially in conscious patient with mild to moderate DKA who can inject himself and even can check his finger stick blood sugar (FS) by use of reliable glucometer was of paramount in managing DKA while reducing the burden on heath staff. This approach actually not new as many studies proved that this approach was effective and safe previously in non-COVID 19 Mild to moderate uncomplicated DKA patients [12] [13] [14] [15] [16]. Studies show that use of lower fluid rate in COVID-19 patient admitted with DKA is important compared to the rate used for non-COVID-19 patients even in patient on steroids they usually increase the insulin doses by 50% rather than fluid rate. Patients with ESRD (End stage renal disease) need lower doses of insulin by nearly half [9] [10].
Many modified DKA approach was published recently. We try to put an algorithm derived from all these published protocols which is easy to apply in Libyan health care systems.
2.1.1. Mild to Moderate DKA
The patient can be managed with subcutaneous insulin approach with use of insulin analogues [9] [10].
The patient should meet all the following criteria to start SQ insulin protocol: [10]
1) Blood gas (venous or arterial) pH ≥ 7.0.
2) Serum bicarbonate ≥ 10 mEq/L.
3) Alert/Awake mental status.
4) MAP > 65 after 1 L IV fluids.
5) K ≥ 3.3 mEq/L.
6) The patient is not. Pregnant, Acute CHF (Congestive heart failure) Exacerbation, Acute Coronary Syndrome, ESRD or CKD Stage 4 or 5, Acute Liver Failure or Cirrhosis, Anasarca, Weight > 120 kg, High-dose Corticosteroids. In all these patients, you can use the same fluid rate and electrolyte correction but with Iv insulin protocol with either increase 50% insulin dose in obese and patient on high steroid or decrease to half dose in patient with ESRD and Liver cirrhosis.
Note: Patients who are stable ESRD and patient on lower steroid dose may be safely managed with SQ insulin approach.
The approach is illustrated in Figure 1.
2.1.2. Patient with Severe DKA
The main difference in the management is the use of IV insulin protocol and higher fluid rate starting with 1 L/first hour and then to rate 200 - 400 ml/hour according to fluid status. The approach is illustrated below [9] [10] (Figure 2).
2.1.3. Management of Electrolyte
Replace Potassium K+ if less than <5.1 mEq/L, Magnesium Mg+ if less than <1.5, Phosphorous Ph if less than <1, Always correct Sodium Na+ for hyperglycemia and change the fluid type accordingly to either 0.45 NS or free water. Table 1 illustrates potassium replacement rate [10].
Figure 1. Management of mild to moderate DKA in COVID-19 patients. Adopted from MSHS COVID-19 DKA Protocol [9].
Figure 2. Management of severe DKA in COVID-19 patients. Adopted from MSHS COVID-19 DKA and Montefiore DKA Protocol. (gtt.: Abbreviation meaning drops)
Table 1. Management of potassium in COVID-19 patients. Adopted from Montefiore DKA protocol.
2.2. Management of Hyperglycemia in Critically Ill Patient without DKA
Generally, the target is to keep the blood sugar in range of 140 - 180 mg/dl with minimal or no hypoglycemia [5] [17]. The preferred way is by using SQ approach with basal and correction doses unless the patient is hemodynamically unstable, on TPN (total parenteral nutrition making his insulin doses unstable) where insulin infusion protocol is needed with blood glucose every one hour is mandatory [7].
When the patient becomes hemodynamically stable change the patient to basal-correction doses as soon as possible to limit the nurse contact. The initial dose of subcutaneous insulin administration at the time of transition can be determined as 60% - 80% of the insulin administered intravenously during the preceding 24 h. To avoid rebound hyperglycemia after transition, a sufficient duration of overlap with the insulin infusion and the subcutaneous insulin administration is required. Short-acting insulin can be administered 1 to 2 h and long-acting insulin 2 to 3 h prior to discontinuation of intravenous insulin administration [7].
Patients who are hemodynamically stable and not on high dose steroid at admission better to be managed with basal-correction doses or even basal-bolus, with correction doses with blood glucose monitored every 4 - 6 hours preferably by finger stick [7].
3. Management of Hyperglycemia in Non-Critically Ill Patient in General Ward
The glycemic target is 110 - 180 mg/dl in most of patients but a level of 110 - 140 mg/dl is reasonable if can be reached without significant hypoglycemia [7].
3.1. Patient Who Is Not Taking Orally [18]
T1D (Type 1 diabetes).
T2D (Type 2 diabetes) on oral or insulin therapy.
Unknown with Admitted BG > 180 mg/dl.
In all these patients use basal-correction insulin doses and follow BG every 4 - 6 hrs.
3.2. Patient Who Is Taking Orally
Use basal-bolus plus correction doses and they should check BG before meals and at bed time.
Type 2 diabetics who was well controlled on diet control and there admitted BG < 180 can be managed in the first 24 hrs. With correction doses only to calculate their insulin requirements and then you can step up to adding basal insulin or basal bolus according to his oral intake.
How to calculate basal bolus regimen:
1) Patients who were on this regimen as outpatients and was with good glycemic control continue in hospital with same dose and adjust according to Finger stick sugar (FS).
2) Patients who are insulin naïve Total daily dose (TDD) calculated at 0.4/kg/day [7].
3) Patients with higher risk of hypoglycemia like patient with renal dysfunction, autonomic neuropathy, liver disease, cardiac disease. Elderly above >65 years, hypoglycemia unawareness their TDD should be calculated at 0.2/kg/day [7].
4) If human insulin is used the TDD should be divided into 4 portions (25% each), three before each meal of regular insulin and one basal NPH [19].
5) If analogues are used the TDD should be divided 50% basal analogues (Glargine 100 IU, Glargine 300 IU, detemir or Tresiba) and 50% of prandial insulin [19].
6) Prandial insulin analogues (Aspart, Lispro, Glulisine) which further divided into three doses equal before each meal.
How to calculate correction doses:
In patient who is NPO or not eating correction doses should be used in addition of basal insulin. Basal insulin is calculated as above. Correction doses calculated depending on blood glucose each 4 - 6 hrs using the following formula:
The patient blood glucose—120/Correction factor.
Correction factor is depending on the TDD. Correction factor indicates the decrease in blood glucose (mg/dl) expected with 1 unit of short acting insulin.
The correction dose is also required in patient who is eating to adjust for the Pre-meal blood glucose if more than 200 mg.
The following table shows the correction factor for each TDD insulin requirement per KG body weight [7] (Table 2).
Table 2. The correction factor for each TDD insulin requirement per KG body weight. Adopted from Bhawna et al., Diabetes Ther (2020).
Note: Patient who is in transition from Insulin infusion should be managed with either Basal, correction doses if he is not eating or basal, bolus with correction if he starts to eat [20].
4. Oral Anti-Diabetic Therapy in Hospitalized Patient with COVID-19
As regard to use of oral therapy in hospitalized COVID-19 patients, the data are either not enough to justify safety or showing harmful effects. However, DDP4 inhibitor has reasonable evidence that supports its use in patient with mild to moderate COVID-19 infection in addition to basal insulin in absence of significant organ function defect [21]. Most of this evidence comes from studies conducted in non-COVID patients [22] [23]. Of note two recent studies show no positive prognostic outcome from the use of DPP4I in type 2 diabetics before admission with COVID-19 infection [24] [25]. Sulphonyl urea, Thiazolidinedione’s (TZD), Metformin, SGLT2 inhibitors all should be discontinued in hospital [26].