Type of oral antidiabetic and non-insulin injectable therapy
Day before surgery
Day of surgery
Patient for AM surgery
Patient for PM surgery
Acarbose
No dose change
Omit morning dose
Give morning dose if eating
Meglitinide
Metformin
No dose change unless contraindications
Sulphonylurea
No dose change
Omit morning dose
Omit morning and evening dose
Pioglitazone
No dose change
DPP-IV inhibitor
DPP-IV inhibitor and GLP-1 recpetor agonist should be omitted on day of surgery
GLP-1 receptor agonist
Omit on day of surgery
SGLT-2 inhibitor
Omit on day before surgery
Some authors suggest that it is not necessary to discontinue oral antidiabetic and non-insulin injectable medications before the day of the surgical procedure, but these medications should not be taken on the day of surgery until normal food intake is restored [37, 39]. Furthermore, a recent study suggests that a preoperative adjustment of home diabetic medications and systematic treatment of perioperative hyperglycemia are safe and could be more effective than the usual care for patients with diabetes undergoing ambulatory surgery [51]. However, the recent Endocrine Society clinical practice guideline recommends the discontinuation of oral and non-insulin injectable antidiabetic agents for the management of hyperglycemia in most non-critical hospitalized diabetic patients, including those undergoing surgery, and the management of hyperglycemia with insulin during admission, including during the perioperative period [45].
8.6.2 Perioperative Management of Patients Treated with Insulin
It is important to note that the current management of insulin treatment in hospitalized patients is no longer based on the concept of correcting the blood glucose of the patient. This out-dated concept includes the use of the well-known, and still used in many settings, sliding scale subcutaneous regular insulin (SSI) regimen. Current practices should include the anticipation of blood glucose excursions of the patient blood glucose profile. In the perioperative setting, this anticipatory action implies the use of the variable rate intravenous insulin infusion (VRIII) in patients who are anticipated to have a long fasting period (more than one missed meal) and in patients with poorly controlled diabetes [36]. The VRIII includes the infusion of intravenous rapid-acting insulin at a variable rate according to regular capillary blood glucose measurements with the aim of controlling serum glucose levels within a specified range, as well as its tendency to increase or decrease. Regular insulin is the most commonly used in VRIII. However, other rapid-acting insulins as aspart, glulisine or lispro insulin, can also be used as alternative and have licence for intravenous use, although these are more expensive alternatives [52]. The VRIII is usually accompanied by an infusion of fluid that contains glucose to prevent insulin-induced hypoglycaemia [52].
There is also insufficient evidence regarding the perioperative management of insulin-treated diabetic patients undergoing surgery. Consequently, the recommendations are based on safety, the avoidance of hypoglycaemia, and the maintenance of adequate glucose control [37]. Recent guidelines recommend maintenance of the usual patient insulin regimen, regardless of a reduction or not of the insulin dose; however, they do not recommend the use of an SSI four times daily as a preoperative treatment [36, 38]. General recommendations for each type of insulin treatment management during the perioperative period for surgeries with a short fasting period (defined as no more than one missed meal) are summarized in Table 8.2.
Table 8.2
Perioperative management of patients treated with insulin for surgeries with a short fasting period
Type of insulin therapy | Day before surgery | Day of surgery | |
|---|---|---|---|
Patient for AM surgery | Patient for PM surgery | ||
Continuous subcutaneous insulin infusion | No dose change or Reduce 20–30 % of basal rate if history of hypoglycaemia | ||
Long-acting insulin analogues | No dose change or Reduce 20–30 % of evening dose if history of nocturnal or morning hypoglycaemia. | No dose change or Reduce 20–30 % of morning dose if history of hypoglycaemia | |
Intermediate-acting insulins | No change of morning dose or Reduce 20–30 % of evening dose | Reduce 25–50 % of morning dose No change of meal evening dose | |
Prefixed combination of insulins | No dose change | Reduce 25–50 % of morning dose of intermediate-acting insulin component. Omit short-acting insulin component in the morning Omit lunchtime dose No change of meal evening dose | No change of morning dose Omit lunchtime dose Leave the evening meal dose unchanged |
Short and rapid-acting insulins | No dose change | Omit morning and lunchtime dose | |
There are insufficient data from fair quality studies concerning the use of insulin treatment during the perioperative period in insulin-naïve patients with DM. In ambulatory surgeries, the SAMBA guidelines suggest that perioperative insulin treatment should be considered in this type of patient in the case of significantly increased glucose levels [37].
8.6.2.1 Long-Acting Insulin Analogues
Long-acting insulin analogues, such as glargine, degludec or detemir insulin, are generally used to maintain blood glucose control between meals. Patients may not experience an increased risk of hypoglycaemia with these treatments even if meals are missed, as observed in preoperative and postoperative fasting.
It remains debated whether doses of long-acting insulin analogues in those patients treated with this type of insulin should be reduced. If the dose of insulin prior to surgery is regarded as adequate, the NHS and SAMBA guidelines recommend the administration of the usual morning or evening dose of long-acting insulin analogue both the previous day and the day of surgery unless there is a history of hypoglycaemia or limited food intake on the day before surgery [36–38]. Other authors recommend reducing the dose of long-acting insulin analogues by 20–30 % in the evening dose the day before surgery and in the morning dose on the day of surgery [39].
A recent randomized trial evaluated three different strategies of long-acting insulin analogue dosing on the evening before surgery (80 % of the usual dose, the dose recommended by a physician, or a dosing table depending on the fasting glucose range and the presence or absence of rapid/short-acting insulin in the daily regimen) and showed no differences among the three groups in the achievement of the fasting blood glucose target [53]. Although this study has several limitations, it is an important step in the management of patients with diabetes undergoing elective surgery. Thus, clinical protocols might be adapted according to local clinical practice.
8.6.2.2 Other Types of Insulin
Combined treatment using insulin and oral antidiabetic drugs, treatments using intermediate-acting or premixed insulins may cause hypoglycaemia while fasting. In relation to intermediate-acting insulins such as Neutral Protamine Hagedorn (NPH) or Neutral Protamine Lispro (NPL) insulin, it is not necessary to change the dose if the medication is taken in the daytime; however, some authors recommend a 25 % reduction of this dose if it is taken in the evening, especially if the patient has a history of hypoglycaemia. On the day of surgery, it is recommended that the morning dose be reduced by 25–50 % [37]. Premixed insulins are a type of fixed combination of rapid-acting and intermediate-acting insulin. It is not necessary to change the dose of premixed insulins the day before surgery. However, premixed insulins should be changed to an intermediate-acting and a rapid-acting insulin on the day of the surgery to prevent hypoglycaemia, with each type of insulin dose administered independently [39] and a reduction of the corresponding proportional morning dose of intermediate-acting insulin by 25–50 % [37–39]. In currently used insulin treatment schedules, short-acting insulin is used to manage meal-induced glycaemic excursions. In relation to these rapid-acting insulins, such as aspart, glulisine, lispro and regular insulin, it is recommended that the dose remain unchanged the day before surgery [37–39]. In addition, it is intuitive to avoid administering the dose while the patient is fasting during the day of surgery due to the postprandial glucose control and potential to increase the risk of hypoglycaemia during fasting.
8.6.3 Intraoperative Treatment to Maintain Glycaemic Control
Classically, glycaemic control has been achieved with the administration of intravenous infusions of insulin and glucose and later of glucose, insulin and potassium (GIK). More recently, insulin has been administered independently, using a VRIII, while glucose and potassium are administered via a volumetric pump to allow better blood glucose control and dose adjustment flexibility. However, the use of VRIII has potential risks, such as hyper and hypoglycaemia due to inappropriate insulin infusion rates or inadequate monitoring, rebound hyperglycemia and potential ketoacidosis if intravenous access is lost or VRIII is terminated inappropriately (especially in patients with type 1 diabetes), as well as infections related to the intravenous line [36, 38, 52]. To prevent these possible secondary effects, it is crucial to maintain strict glucose monitoring and to increase or decrease the insulin infusion rate, and even to stop it and reassess the glucose values in cases presenting a risk of severe hypoglycaemia. It is important to take into account that the interruption of insulin infusion in patients with type 1 compared with type 2 diabetes is associated with a greater potential risk of ketoacidosis due to the lack of a pancreatic insulin reserve. Because of these issues, many units currently manage the perioperative glucose control of diabetic patients by modifying their usual treatment, although successful modification of the usual treatment for DM can only be utilized if the fasting period is short, surgery can be carried out early, previous metabolic control of DM is acceptable (HbA1c <8.5 % at admission) and the patient will be capable of self-managing his DM during the immediate post-operative period. If these criteria are not present then VRIII should be initiated [36, 38].
8.6.3.1 Surgeries with a Short Fasting Period
There is insufficient evidence to recommend a safe and effective treatment strategy to achieve target blood glucose levels in diabetic patients undergoing surgery with a short fasting period, which is defined as no more than one missed meal. This is the case in, for example, ambulatory surgical procedures [37].
The NHS guidelines recommend that patients undergoing surgeries with a short fasting period should be managed by a modification of their usual antidiabetic medication, including insulin, avoiding a VRIII regimen whenever possible [36, 38]. There are insufficient data to recommend the use of regular or rapid-acting insulin analogues in diabetic ambulatory surgical patients. However, the SAMBA guidelines suggest the use of subcutaneous rapid-acting insulin analogues rather than regular insulin [37] to correct hyperglycemia due to their pharmacokinetic properties and shorter duration of observation requirements in the postoperative period.
Although the intravenous infusion of rapid-acting insulin has been used to maintain optimal blood glucose levels in patients undergoing major surgeries, recent guidelines recommend the subcutaneous route for noncritical patients [44, 45]. The SSI regimens are commonly used in clinical practice, but they have been questioned recently [44, 45]. For all of these reasons, it is recommended that subcutaneous rather than intravenous insulin administration be applied in diabetic patients undergoing ambulatory surgery to achieve intraoperative glucose control [37]. In cases in which the blood glucose levels cannot be maintained adequately below 216 mg/dl (12 mmol/l), it is recommended to consider changing to a VRIII [38].
8.6.3.2 Surgeries with a Long Fasting Period
Surgeries that require hospital admission are typically associated with a long fasting period, which is defined as more than one missed meal, and VRIII treatment. An adequate glucose supply should be provided to prevent the induction of a catabolic state, starvation ketosis, and insulin-induced hypoglycaemia. VRIII is often poorly used in the perioperative setting and requires explicit guidelines such as the NHS guidelines [36, 38]. The initial insulin infusion should be determined by capillary blood glucose (CBG). There are multiple and a different recommendations of VRIII initiation and one example is described in Table 8.3. It is recommended that the CBG be measured hourly. If the CBG remains above 216 mg/dl (12 mmol/l) for three consecutive readings and is not dropping by 54 mg/dl/h (3 mmol/l/h) or more, the rate of insulin infusion should be increased. If the CBG is less than 72 mg/dl (4 mmol/l), then the rate of insulin infusion should be reduced [38]. The judgement of the clinician is also important in cases in which hypoglycaemia is considered to increase the risk of adverse events for the patient, and the alternative should include the decision to stop the insulin infusion for a short period (for instance, 30 min) with a subsequent re-assessment of CBG to determine the new infusion rate. The VRIII must be administered continuously with a concomitant glucose and electrolyte infusion substrate, using a pump adjacent to the substrate infusion. Insulin must be infused at a variable rate to maintain the blood glucose between 108 and 180 mg/dl (6–10 mmol/l). If the infusion is stopped, no exogenous insulin will be present in the circulation after 3–5 min.
Table 8.3
Suggested intraoperative variable rate intravenous insulin infusion recommendation for a diabetic patient
How to set up an intravenous insulin infusion: |
1 mL of rapid-acting insulin (100 IU) + 99 mL of 0.9 % saline solution |
Concentration of 1 IU rapid-acting insulin/mL of solution |
Types of rapid-acting insulins: |
Regular insulin is the most commonly used in VRIII but other types, as aspart, glulisine and lispro insulin, can also be used |
Glucose target: |
108–180 mg/dl (6–10 mmol/l), acceptable 72–216 mg/dl (4–12 mmol/l) |
Different scales for variable rate intravenous insulin infusion | |||
|---|---|---|---|
Glucose mg/dl (mmol/l) | Insulins rates (ml/h) | ||
Reduced rate | Standard rate | Increased rate | |
<72 mg/dl (<4 mmol/l) | 0 | 0 | 0 |
72–144 mg/dl (4–8 mmol/l) | 0.5 | 1 | 2 |
145–216 mg/dl (8.05–12 mmol/l) | 1 | 2 | 4 |
217–288 mg/dl (12.05–16 mmol/l) | 2 | 4 | 6 |
289–360 mg/dl (16.05–20 mmol/l) | 3 | 5 | 7 |
361–432 mg/dl (20.05–24 mmol/l) | 4 | 6 | 8 |
>432 mg/dl (>24 mmol/l) | 6 | 8 | 10 |
8.6.3.3 Fluid Management
The aims of fluid management in the surgery of a patient with DM are to provide glucose as a metabolic substrate to maintain blood glucose levels, to optimize the intravascular volume status and to maintain serum electrolytes [38]. Adequate preoperative hydration and intraoperative fluid administration are necessary. The daily requirements of major ions and fluid in a healthy adult are 60–100 mmol of sodium, 40–80 mmol of potassium and 1.5–2.5 l of water. These requirements may change in disease states, and careful daily monitoring is needed. There is limited evidence on which to base recommendations for optimal fluid and insulin management in patients with DM undergoing surgery. The guidelines recommend different fluid solutions depending on the need for VRIII. The recommended first choice substrate solution for patients with DM who require VRIII is 0.45 % sodium chloride with 5 % glucose and 0.15–0.3 % potassium chloride (KCl). In the rare case that the patient develops hyponatremia, a 0.9 % saline infusion containing 5 % glucose and 0.15–0.30 KCl is recommended [36, 38]. The recommended substrate solution for diabetic patients who do not require VRIII is Hartmann’s solution, which is preferred over 0.9 % saline sodium chloride to reduce the risk of hyperchloremic acidosis. It has been suggested that Hartmann’s solution may lead to hyperglycemia in patients with type 2 diabetes. However, 1 l of Hartmann’s solution increases the plasma glucose no more than 1 mmol/l [54]; thus, it is in fact not contraindicated in diabetic patients.
Glucose and insulin infusions can provide good glycaemic control but may lead to hyponatremia. Surgical patients with DM are not only at risk of complications associated with fluid and electrolyte management, but are also at an elevated risk of hyponatremia due to the use of hypotonic glucose solutions.
8.6.4 Perioperative Blood Glucose Monitoring
Adequate monitoring of the CBG concentration is necessary to maintain patient safety, correct hyperglycemia, detect hypoglycaemia and modify the insulin treatment if necessary [38]. Although the perioperative CBG ranges are controversial, as discussed above, the WHO recommends a surgical safety target of blood glucose between 108 and 180 mg/dl (6–10 mmol/l), with a range that is considered acceptable from 72 to 216 mg/dl (4–12 mmol/l). In ambulatory surgeries, it has been suggested that blood glucose levels should be evaluated prior to surgery when the patient arrives at the clinic and before his or her discharge home [37]. Although there are no recommendations for specific procedures, the guidelines recommend assessing CBG prior to the induction of anaesthesia and regularly monitoring it during the procedure and in the immediate postoperative period, at least hourly when the blood glucose is stable and in the target range, depending on the duration of surgery and the type of insulin administered [38]. If the blood glucose level changes or the patient is receiving intraoperative insulin, then more frequent glucose measurements might be required.
8.6.5 Immediate Postoperative Management
The aims of postoperative care include to ensure glycaemic control and maintain the fluid and electrolyte balance, optimize pain control (adequate pain relief decreases catabolic hormone secretion), encourage an early return to normal eating and drinking by managing nausea and vomiting, facilitate return to the usual diabetes treatment regimen and avoid iatrogenic effects.
Glucose control during the postoperative period may be unpredictable and difficult, and there is insufficient evidence to support the guideline recommendations. The Endocrine Society clinical practice guideline on the management of hyperglycemia in hospitalized patients does not recommend prolonged use of an SSI regimen for hyperglycemic control during the postoperative period in patients with DM [45] based on the RABBIT 2 Surgery Study results. This prospective randomized study in patients with type 2 diabetes undergoing surgery revealed an improvement in glycaemic control and a reduction in postoperative complications with a bolus-basal treatment compared with an SSI [55].
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