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A practical approach to managing diabetes in the perioperative period.

The burden of non-communicable disease in South Africa (SA) is escalating. Undiagnosed and uncontrolled diabetes mellitus (DM) are common in patients requiring surgery. Access to resources and expertise to safely control blood glucose levels in the perioperative period are variable in the SA public healthcare system. The combination of an increasing burden of disease and inadequate perioperative diabetes management is likely to increase surgical complication rates, mortality and cost of care.

This article focuses on perioperative diabetes management of type 1 and type 2 DM patients who are undergoing surgery in a noncritical care setting. Obstetric, paediatric and critical care patients are excluded from this discussion.

Burden of disease

Type 2 DM is the most common type of diabetes, representing >90% of the DM disease burden in SA. The International Diabetes Federation reports that there are currently ~1.8 million adults in SA known to have DM, while a further 1.5 million adults remain undiagnosed. [1] The SA National Health and Nutrition Examination Survey (SANHANES) 2012 showed a national prevalence of abnormal glucose regulation of 18.6%, varying according to ethnicity and degree of urbanisation. According to SANHANES, 45% of people with diabetes were previously undiagnosed. [2]

Over the past decade, DM has become one of the major underlying causes of mortality globally; in SA it now ranks second only to tuberculosis. [3]

The SA Surgical Outcomes Study (SASOS) reports a 10.2% prevalence of diabetes in our surgical population (5.8% non-insulin dependent, and 4.4% insulin dependent). [4]

Diabetes mellitus in the perioperative context

The perioperative period is associated with worsening glycaemic control, probably due to the stress response of surgery. [5] Starvation, tissue trauma and pain lead to increased levels of pro-inflammatory mediators and circulating stress hormones. These substances alter insulin secretion and sensitivity, producing a state of relative insulin resistance, protein catabolism and lipolysis with liberation of free fatty acids. This state can extend for multiple days into the postoperative period, driving adverse patient outcomes. [6] These include increased mortality, increased length of hospital stay, as well as increased infective (surgical site infections, urinary tract infections and pneumonia) and non-infective complications (cardiac events, acute kidney injury and stroke). [7]

Protocol-driven quality improvement projects result in improved perioperative glycaemic control, but strict control strategies increase hypoglycaemic events. [8,9] As hypoglycaemia has been linked to mortality, it is essential to avoid the condition by targeting a perioperative blood glucose level in the range of 6.0-10.0 mmol/L. [10] A capillary blood glucose (CBG) measurement up to 12.0 mmol/L may be tolerated for brief periods if it is regularly monitored and expected to decrease. [11,12]

Hyperglycaemia in the perioperative period may be due to physiological stress and should not be diagnosed as DM without input from the local diabetes healthcare provider. Stress hyperglycaemia without DM is a poorly understood entity, the management of which remains unclear. [5]

Perioperative management

Consider perioperative management of DM in three phases: preoperative, intraoperative, and postoperative.

Preoperative

In the preoperative phase the patient with DM must be identified and assessed to define a perioperative management plan. Screen for undiagnosed DM according to the Society for Endocrinology, Diabetes and Metabolism of SA (SEMDSA) guidelines. [13] Evaluate the diabetic patient's capacity to manage the disease, chronic glycaemic control and invasiveness of the planned surgery. Where available, a glycated haemoglobin (HbA1c) should be used to determine adequacy of glycaemic control in those diagnosed with diabetes. An elevated HbA1c correlates with poor patient outcomes after surgery and an HbA1c >8.5% (69 mmol/mol) warrants postponement of elective surgery. [11,12] More stringent cut-off values are recommended by some, but may currently be unattainable in many parts of SA. [14]

The patient's comorbidities and glycaemic control should always be optimised before elective surgery. In an emergency, there is little time for optimisation, as surgery must proceed promptly. Often though, patients present for surgery that is time sensitive. In this 'grey zone' between elective and emergency, the timing of surgery should be determined by a multidisciplinary team with a patient-centred discussion about how best to balance risk and benefit. [15] The decision to proceed with surgery in the face of uncontrolled DM must acknowledge the increased risk to the patient and define ways to manage this risk.

Resources and access to expertise vary among healthcare centres. It is therefore important to choose an appropriate perioperative glycaemic management plan. Although many options are available, four are commonly used and recommended (Table 1):

* modification of usual treatment (Tables 2 and 3)

* basal-bolus subcutaneous (SC) insulin (Fig. 1)

* Alberti's glucose-insulin-potassium (GIK) intravenous infusion (Box 1)

* variable rate intravenous insulin infusion (VRIII) (Fig. 2).

Monotherapy with SC short- or rapid-acting insulin according to a sliding scale is not recommended for in-hospital management of

DM, as it increases the risk of hypoglycaemia and provides inferior glycaemic control. [16,17]

In all cases, limiting of the starvation period has to be planned, as well as where the patient will be managed postoperatively (day case, surgical ward or high-care facility). For short starvation periods (one missed meal), modification of the usual medication will often suffice (Tables 2 and 3). Missing more than one perioperative meal is considered a prolonged starvation period. If the CBG is >12 mmol/L, it will necessitate either basal SC insulin or an intravenous insulin infusion.

Intraoperative

The intraoperative phase starts at the time of arrival in theatre and continues until transfer to the postoperative ward. The patient with DM must have a documented CBG prior to commencement of anaesthesia. While under anaesthesia, the CBG should be monitored at least 2-hourly, more frequently if abnormal and in patients receiving insulin. [18] If the intraoperative CBG levels were abnormal, the CBG measurement should be repeated in the post-anaesthetic recovery area.

When possible, administer SC short- or rapid-acting insulin to avoid unnecessary intravenous insulin for short surgical procedures. Limit SC short- or rapid-acting insulin to two intraoperative doses. In type 2 DM, a first dose of 0.1 U/kg (up to a maximum of 6 U) is appropriate; alternatively, use the correction dosing scale in Fig. 1 as a starting point. To prevent insulin stacking intraoperatively, do not administer a top-up dose of SC insulin within 2 hours of the first dose. Intravenous insulin is preferred when SC insulin does not control hyperglycaemia. This is common in surgery of longer duration, prolonged starvation and emergency cases. [11]

Postoperative

After surgery, intravenous insulin therapy must not be discontinued without overlapping and restarting the patient's basal SC insulin. Check the CBG before discharge from the post-anaesthetic recovery area. Ensure that the patient is sent to the appropriate level of care for continuation of their glycaemic control strategy. Early reinstatement of normal enteral feeding and usual antidiabetic medication is the goal. The agents and regimen used for glycaemic control will largely depend on the feeding status of the patient (Table 4).

Safe insulin therapy

Insulin is an extremely potent agent. Drug errors can cause significant harm to the patient. Staff education and involvement of the local pharmacy are needed to ensure constant safe prescribing, dispensing and dosing practices. [19]

There is a real risk of diabetic ketoacidosis (DKA) with transition to and from intravenous insulin therapy. Delays in commencing the intravenous insulin infusion, and discontinuation of the infusion prior to administration of basal insulin, cause acute insulin deficiency in insulin-dependent patients. [20] This risk can be mitigated by continuation of basal SC insulin while using intravenous insulin, or by administration of intermediate- or long-acting insulin 30 minutes before discontinuing the intravenous insulin (GIK or VRIII). [12]

Non-insulin antidiabetic agents

Non-insulin antidiabetic agents should not be started in the immediate perioperative period. These medications have multiple contraindications and are not rapidly titratable. However, diabetic patients who are well controlled could be considered for continuation of their non-insulin agents during the perioperative period. Guidance on the management of these agents during the perioperative period is given in Table 2. Modification of oral therapy as the primary perioperative glycaemic control strategy is only appropriate in uncomplicated surgical patients who miss one meal during the perioperative period. Critically ill patients, those with poor glycaemic control and those who miss multiple meals, should be managed with an appropriate insulin regimen. [21,,22]

Hypoglycaemia

The perioperative period represents an increased risk for undiagnosed hypoglycaemia while patients are fasting and under the influence of sedative agents. Whenever insulin is prescribed in hospital, hypoglycaemia treatment must be prescribed on the same chart. Perioperatively, a CBG <6.0 mmol/L should be interpreted as imminent hypoglycaemia. A CBG <4.0 mmol/L is associated with harm and must be treated. Interruption of insulin therapy is discouraged, but dose reduction may be necessary. Assess the patient with a low CBG for signs and symptoms of hypoglycaemia. Consider their feeding status (eating or fasting) and their risk of hypoglycaemia unawareness. Fig. 3 provides a suggested hypoglycaemia management algorithm. While under the influence of anaesthesia, treat all patients with a low CBG with intravenous dextrose. If the CBG is <6.0 mmol/L, administer 10 g intravenous dextrose; if the CBG is <4.0 mmol/L, give 20 g intravenous dextrose. Thereafter, the CBG should be measured every 15 minutes and treatment repeated until the blood glucose is corrected. [11]

Special circumstances

SC insulin infusion (SCII) (or insulin pump therapy) is increasingly used in the management of type 1 DM. Patients using an insulin pump should, as far as possible, maintain control of their own perioperative glycaemic management. When assessing these patients, consider the invasiveness, duration and site of the surgery, as well as the anticipated postoperative course. Question how many meals the patient will skip. Will the anaesthetist have access to the SCII intraoperatively? Will the device location infringe on the surgical site? Ideally, a preoperative basal test is done to establish glycaemic response to the fasting state. If this was not done, ask the patient to decrease the SCII to 70-80% of the basal rate while fasting. Ensure that the anaesthetic provider understands how to adjust, discontinue and remove the SCII if necessary. If continued intraoperatively, one or two small (2-4 U) SC correctional doses of insulin may be administered if the CBG rises [greater than or equal to] 10.0 12.0 mmol/L. If this fails to correct the CBG, start a VRIII. If the CBG decreases to <4.0-6.0 mmol/L, treat the hypoglycaemia with intravenous dextrose. If hypoglycaemia persists, disconnect the SCII and switch to a VRIII. SCII is not appropriate for emergency surgery or where more than one meal is missed in the perioperative period. [23,24]

For patients with DM, day-case surgery must be considered. [14] It reduces the risk of iatrogenic complications and empowers the patient to manage their own perioperative glycaemic control. When assessing diabetic patients for day-case surgery, three aspects must be considered:

* Is the patient physically, mentally and socioeconomically capable to self-manage their DM and do they have easy access to emergency healthcare should they need it?

* Is their DM adequately controlled, with a recent HbAlc <8.5%?

* Is the nature of the surgery suitable for a day case?

A multidisciplinary contextsensitive approach

No single scenario describes every patient with DM who has to undergo surgery. At each facility (or group of facilities) a representative multidisciplinary team must evaluate the unique patient-resource environment and develop an evidence-based clinical practice guideline that fits their context. Smaller facilities should obtain input from their regional specialist centre.

It is essential to empower patients to self-manage their diabetes, especially in a setting where access to resources or healthcare personnel is limited. When appropriate, patients should be given guidance to manage their own insulin and non-insulin antidiabetic therapy in the ward. [21]

The dietician, or equivalent team member, must engage the kitchen service to ensure that the diabetic diet provides a constant caloric intake from meal to meal and day to day. This will reduce prandial fluctuations in blood glucose and reduce the need for correction doses of insulin. The surgical team should understand the meal plan to ensure that minimal time elapses from the start of preoperative fasting until the first postoperative meal.
Box 1. Alberti glucose-insulin-potassium infusion [21,27]

The GIK infusion is an alternative IV insulin regimen when a VRIII
is not feasible. It provides substrate, IV insulin and electrolytes
via a single infusion.

The original GIK regimen was published by Alberti and Thomas in
1979. It provides a safe and effective method of giving substrate,
IV insulin in the same infusion. Alterations of the original
regimen remain in use today. [28,29,30]

The original GIK regimen uses a bag containing 500 mL 10% dextrose
and adds:

* 10 U short-acting insulin

* 10 mL 10% KCl.

The infusion runs at a fixed rate of 100 mL/h, providing 2 U
insulin per hour.

CBG is measured 1 - 2-hourly. To increase or decrease the insulin
infusion rate by 1 U/h the insulin content of the bag is changed up
or down by 5 U. A new bag must be mixed each time it is decided to
adjust the insulin infusion rate.

Problems with the GIK infusion are:

* labour intensive and wasteful when multiple bag changes are
needed

* maintenance at 100 mL/h exceeds current standards for care of
surgical patients

* 500 mL 10% dextrose bags are not available at all locations

* 10% dextrose water is not an acceptable maintenance fluid

* risk of DKA in type 1 DM if GIK infusion is stopped.

If deemed appropriate for the location, the local multidisciplinary
team must adapt the GIK regimen to suite their context and address
the concerns mentioned. Involve specialist input.

GIK = glucose-insulin-potassium; IV = intravenous; VRIII = variable
rate intravenous insulin infusion; CBG = capillary blood glucose;
DKA = diabetic ketoacidosis; DM = diabetes mellitus.


The local protocol should consider how care will be escalated for selected patients. Every DM patient cannot be referred to a diabetologist. Also define how feedback on perioperative DM management will be used to bring the patient back into the primary healthcare system after the perioperative period.

Conclusion

DM is an ever-growing public health problem affecting patient outcomes after surgery. This article addresses the SA scope of the problem and provides a structure for managing the patient with DM presenting for surgery. A local multidisciplinary team should guide practice at each facility. The recommended reading section provides essential information for individual perioperative providers and teams caring for surgical patients with DM. Where a patient scenario falls outside the scope of this discussion, the provider must consult the local multidisciplinary team or referral specialist centre for guidance.

Key points

* DM is a modifiable risk factor of adverse surgical outcomes. Undiagnosed DM or an HbA1c >8.5% (69 mmol/mol) is an indication to postpone elective surgery.

* Monotherapy using SC short- or rapid-acting insulin according to a sliding scale is not recommended.

* In all patients with DM, attempt to minimise the starvation period to only one missed meal.

* A CBG range of 6.0-10.0 mmol/L is the recommended target in the perioperative period. A CBG up to 12 mmol/L may be acceptable.

* Safe insulin prescribing practice requires prescription of hypoglycaemia treatment on every insulin prescription chart.

* In-hospital interruption of insulin therapy is a common cause of DKA in patients with type 1 DM.

* A multidisciplinary team should drive context-sensitive perioperative management of DM.

Acknowledgements. None.

Author contributions. All authors contributed to the design, research and editing of this manuscript.

Funding. None.

Conflicts of interest. None.

[1.] International Diabetes Federation. IDF Diabetes Atlas. 8th ed. Brussels: IDF, 2017. http://www.diabetesatlas.org (accessed 8 April 2018).

[2.] Shisana O, Labadarios D, Rehle T, et al The South African National Health and Nutrition Examination Survey, 2012: SANHANES-1. Pretoria: Human Sciences Research Council, 2014:477-473.

[3.] Statistics South Africa. Mortality and causes of death in South Africa, 2016: Findings from death notification. http://www. statssa.gov.za/publications/P03093/P0309320165.pdf (accessed 8 April 2018).

[4.] Biccard BM, Madiba TE. The South African Surgical Outcomes Study: A 7-day prospective observational cohort study. S Afr Med J 2015;105(6):465-475. https://doi.org/10.7196/SAMJ.9435

[5.] Davis G, Fayfman M, Reyes-Umpierrez D, et al. Stress hyperglycemia in general surgery: Why should we care? J Diabet Comp 2018;32(3):305-309. https://doi.org/10.1016/j. jdiacomp.2017.11.010

[6.] Duggan EW, Klopman MA, Berry AJ, Umpierrez G. The Emory University perioperative algorithm for the management of hyperglycemia and diabetes in non-cardiac surgery patients. Curr Diab Rep 2016;16(3):34. https://doi.org/10.1007/s11892016-0720-z

[7.] Frisch A, Chandra P, Smiley D, et al. Prevalence and clinical outcome of hyperglycemia in the perioperative period in noncardiac surgery. Diabet Care 2010;33(8):1783-1788. https:// doi.org/10.2337/dc10-0304

[8.] Alexanian SM. Glycemic outcomes three years after implementation of a perioperative glycemic control algorithm in an academic institution. Endocr Pract 2016;23(2):123-231. https://doi.org/10.4158/EP161354

[9.] Buchleitner AM, Martinez-Alonso M, Hernandez M, Sola I, Mauricio D. Perioperative glycaemic control for diabetic patients undergoing surgery. Cochrane Database Syst Rev 201;(9):CD007315. https:// doi.org/10.1002/14651858.CD007315.pub2

[10.] Turchin A, Matheny ME, Shubina M, Scanlon JV, Greenwood B, Pendergrass ML. Hypoglycemia and clinical outcomes in patients with diabetes hospitalized in the general ward. Diabet Care 2009;32(7):1153-1157. https://doi.org/10.2337/dc08-2127

[11.] Barker P, Creasey PE, Dhatariya K, et al. Peri-operative management of the surgical patient with diabetes 2015: Association of Anaesthetists of Great Britain and Ireland. Anaesthesia 2015;70(12): 1427-1440. https://doi.org/10.1111/ anae.13233

[12.] Dhatariya K, Levy N, Hall GM. The impact of glycaemic variability on the surgical patient. Curr Opin Anaesthesiol 2016;29(3):430-437. https://doi.org/10.1097/ACO.0000000000000326

[13.] The Society for Endocrinology, Metabolism and Diabetes of South Africa Type 2 Diabetes Guidelines Expert Committee. Screening and diagnosis of type 2 diabetes and intermediate hyperglycaemia. SEMDSA guideline for the management of type 2 diabetes. J Endocrinol Metab Diabet S Afr 2017;22(1)(Suppl 1):S15-S19.

[14.] Joshi GP, Chung F, Vann MA, et al. Society for Ambulatory Anesthesia consensus statement on perioperative blood glucose management in diabetic patients undergoing ambulatory surgery. Anesth Analg 2010;111(6):1378-1387. https://doi.org/10.1213/ANE.0b013e3181f9c288

[15.] Levy N, Penfold NW, Dhatariya K. Perioperative management of the patient with diabetes requiring emergency surgery. BJA Educ 2016;17(4):129-136. https://doi.org/10.1093/bjaed/mkw056

[16.] Jaram MK. Hyperglycaemia management of type 2 diabetes mellitus inpatients in surgical wards at Livingstone Hospital. S Afr Pharmaceut J 2016;83(8):52-55.

[17.] Hirsch IB. Sliding scale insulin - time to stop sliding. JAMA 2009;301(2):213-214. https://doi.org/10.1001/ jama.2008.943

[18.] Sebranek JJ, Lugli AK, Coursin DB. Glycaemic control in the perioperative period. Br J Anaesth 2013;111(Suppl 1):i18-i34. https://doi.org/10.1093/bja/aet381

[19.] Hellman R. A systems approach to reducing errors in insulin therapy in the inpatient setting. Endocr Pract 2004;10(Suppl 2):100-108. https://doi.org/10.4158/EP.10.S2.100

[20.] National Diabetes Inpatient Audit England and Wales. 2016. http://www.digital.nhs.uk/pubs/ nadia2016 (accessed 8 April 2018).

[21.] Dhatariya KLN, Flanagan D, Hilton L, Kilvert A, Rayman G, Watson B. Management of adults with diabetes undergoing surgery and elective procedures: Improving standards. http://www.diabetologistsabcd.org.uk/JBDS/JBDS_IP_Surgical_Guideline_2015_Full.p df (accessed 8 April 2018).

[22.] Stubbs DJ, Levy N, Dhatariya K. Diabetes medication pharmacology. BJA Educ 2017;17(6):198-207. https://doi.org/10.1093/bjaed/mkw075

[23.] Draznin B. Managing Diabetes and Hyperglycemia in the Hospital Setting: A Clinician's Guide. Virginia: American Diabetes Association, 2016. https://doi.org/10.2337/9781580406086

[24.] Partridge H, Perkins B, Mathieu S, Nicholls A, Adeniji K. Clinical recommendations in the management of the patient with type 1 diabetes on insulin pump therapy in the perioperative period: A primer for the anaesthetist. Br J Anaesth 2016;116(1):18-26. https://doi.org/10.1093/bja/aev347

[25.] Umpierrez GE, Smiley D, Jacobs S, et al Randomized study of basal-bolus insulin therapy in the inpatient management of patients with type 2 diabetes undergoing general surgery (RABBIT 2 surgery). Diabet Care 2011;34(2):256-261. https://doi.org/10.2337/dc10-1407

[26.] The Society for Endocrinology, Metabolism and Diabetes of South Africa Type 2 Diabetes Guidelines Expert Committee. In-hospital management of hyperglycaemia. SEMDSA guideline for the management of type 2 diabetes. J Endocrinol Metab Diabet S Afr 2017;22(1)(Suppl 1):S68-S73.

[27.] Alberti K, Thomas D. The management of diabetes during surgery. Br J Anaesth 1979;51(7):693-710. https://doi.org/10.1093/bja/51.7.693

[28.] Polderman JA, Steen SC, Thiel B, Godfried MB. Peri-operative management of patients with type2 diabetes mellitus undergoing non-cardiac surgery using liraglutide, glucose- insulin-potassium infusion or intravenous insulin bolus regimens: A randomised controlled trial. Anaesthesia 2018;73(3):332-339. https://doi.org/10.1111/anae.14180

[29.] Kayes MN, Prodhan NK, Malik RH. Perioperative management of diabetes: A review. Delta Med Coll J 2014;2(2):71-76. https://doi.org/10.3329/dmcj.v2i2.20528

[30.] Khan NA, Ghali WA, Cagliero E. Perioperative management of blood glucose in adults with diabetes mellitus. UpToDate. http://www.uptodate.com (accessed 8 April 2018).

Recommended reading

Barker P, Creasey PE, Dhatariya K. Peri-operative management of the surgical patient with diabetes. Anaesthesia 2015;70(12):1427-1440. https://doi.org/10.1111/anae.13233

Hirsch IB. Sliding scale insulin - time to stop sliding. JAMA 2009;301(2):213- 214. https://doi.org/10.1001/ jama.2008.943

Safer insulin prescribing. http://nice.org.uk/guidance/ktt20 (accessed 8 April 2018).

Stubbs DJ, Levy N, Dhatariya K. Diabetes medication pharmacology. BJA Educ 2017;17(6):198-207. https:// doi.org/10.1093/bjaed/mkw075

The Society for Endocrinology, Metabolism and Diabetes of South Africa Type 2 Diabetes Guidelines Expert Committee. The 2017 SEMDSA guideline for the management of type 2 diabetes. J Endocrinol Metab Diabet S Afr 2017;22(1)(Suppl 1):S1-S196.

Umpierrez GE, Smiley D, Jacobs S. Randomized study of basal-bolus insulin therapy in the inpatient management of patients with type 2 diabetes undergoing general surgery (RABBIT 2 surgery). Diabet Care 2011;34(2):256-261. https://doi.org/10.2337/dc10-1407

Accepted 3 April 2018.

L du Toit, (1) MB ChB, FCA (SA), MMed (Anaes); T Biesman-Simons, (1) MB ChB, DA (SA); N Levy, (2) MBBS, BSc, FRCA, FFICM; J A Dave, (3) MB ChB, PhD, FCP (SA), Cert Endocrinology (SA)

(1) Department of Anaesthesia and Perioperative Medicine, Groote Schuur Hospital, Cape Town, South Africa

(2) Department of Anaesthesia and Perioperative Medicine, West Suffolk Hospital, UK

(3) Division of Endocrinology and Diabetic Medicine, Groote Schuur Hospital, Cape Town, South Africa

Corresponding author: L du Toit (leon.alive@gmail.com)
Table 1. Indications, advantages and disadvantages of four
perioperative diabetes management strategies

Management        Indications                Advantages

Modification of   HbA1c <8.5%                Lowest risk for
usual therapy     Short starvation period    hypoglycaemia
                  (<1 meal missed)           Decreased burden on ward
                                             staff
                                             Suitable for patient
                                             self-management

Basal-bolus SC    Those already on basal-    Improved glycaemic
insulin with      bolus insulin              control
correction        Type 1 diabetes            Flexible dosing
doses             Patients with poor         Decreased risk of
                  baseline control           hypoglycaemia
                  Newly diagnosed DM
                  requiring perioperative
                  insulin therapy
                  Short surgical duration
                  Where IV insulin therapy
                  is not feasible

Alberti's         Poor control on SC         Improved glycaemic
glucose-          insulin (CBG >12.0         control
insulin-          mmol/L)                    Flexible
potassium         Prolonged starvation
infusion          period (>1 meal missed)
                  Long surgical duration
                  Periods of inadequate
                  tissue perfusion
                  High-care or ICU setting
                  VRIII is not an option

VRII              Poor control with SC       Improved glycaemic
                  insulin (CBG >12.0         control
                  mmol/L)                    Flexible
                  Prolonged starvation
                  period (>1 meal missed)
                  Long surgical duration
                  Periods of inadequate
                  tissue perfusion
                  High-care or ICU setting

Management        Disadvantages

Modification of   Often not possible, as patients have
usual therapy     poor baseline control or there is
                  prolonged starvation

Basal-bolus SC    Intensive
insulin with      Regular monitoring required
correction        Not to be used if the patient is not
doses             eating meals
                  Unpredictable absorption when there
                  is impaired tissue perfusion

Alberti's         Labour intensive
glucose-          Need trained staff
insulin-          Risk of hypo-[Na.sup.+]/[K.sup.+]
potassium         Risk of hypoglycaemia
infusion

VRII              Requires specialised equipment
                  Labour intensive
                  Need trained staff
                  Risk of hypo-[Na.sup.+]/[K.sup.+]
                  Risk of hypoglycaemia

SC = subcutaneous; DM = diabetes mellitus; IV = intravenous; CBG =
capillary blood glucose; ICU = intensive care unit; VRIII = variable
rate intravenous insulin infusion.

Table 2. Summary of non-insulin antidiabetic agents with
recommendations for perioperative management [21,22]

                Class of drug
Management      (examples)          Considerations      Recommendations

Insulin         Biguanides          Does not cause      Continue while
sensitisers       Metformin           hypoglycaemia       eating
                                    Risk of lactic      Omit on day of
                                      acidosis            surgery
                                                        Omit if risk of
                                                          renal
                                                          impairment
                                                          (IV contrast,
                                                          other
                                                          nephrotoxic
                                                          agents,
                                                          haemodynamic
                                                          instability)
                                                        Omit if >1 meal
                                                          missed
                Thiazolidinediones  Does not cause      Omit on day of
                Pioglitazone          hypoglycaemia       surgery
                  (roziglitazone)   Concern of          Restart when
                                      hepatotoxicity      tolerating
                                      Contraindicated     meals
                                      in haemodynamic
                                      instability

Secretagogues   Sulphonylureas      Risk of             Omit while
                  Glibenclamide       hypoglycaemia       fasting
                  Gliclazide                            Restart when
                  Glimepiride                             tolerating
                                                          meals
                Meglitinides        Risk of             Omit while
                  Repaglinide         hypoglycaemia       fasting
                  Nateglinide                           Restart when
                                                          tolerating
                                                          meals
Incretin        GLP-1 analogues     Delayed gastric     Limited
family            Exenatide           emptying concern    information
                  Liraglutide         for aspiration    May improve
                                      risk                perioperative
                                    Injectable only       glycaemic
                                                          control
                DPP-4 inhibitors                        Limited
                  (gliptins)                              information
                  Saxagliptin                           May improve
                  Vildagliptin                            perioperative
                                                          glycaemic
                                                          control
Increased       SGLT-2 inhibitors   Association         Avoid in the
glucosuria      (gliflozins)          with DKA            perioperative
                  Empagliflozin                           period
                  Dapagliflozin

Impairs         Alpha-glucosidase   Causes severe       Avoid in the
absorption        inhibitors          flatulence          perioperative
                  Acarbose            and bloating        period

GLP-1 = glucagon-like peptide 1; DPP-4 = dipeptidyl peptidase-4; SGLT-
2 = sodium-glucose co-transporter 2; DKA = diabetic ketoacidosis; IV =
intravenous.

Table 3. Perioperative modification of insulin therapy * ([dagger])

Insulin regimen *         Day before surgery     Day of surgery
([double dagger])

Once daily (evening       Reduce dose by 20%     Restart insulin with
  dosing) intermediate-                            evening meal
  or long-acting
  insulin
Once daily (morning       Usual dose             Reduce dose by 20%
  dosing) intermediate-
  or long-acting
  insulin
Twice daily dosing        Usual dose             Reduce morning dose
                                                   to 50%
Premixed insulin, or                             Normal evening dose
  intermediate-or long-                            with dinner
  acting insulin
Basal-bolus regimen       Usual bolus doses      If basal dose in the
                                                   morning, reduce by
                                                   20%
                          Reduce night-time      Omit bolus doses
                            basal dose by 20%      while fasting

* Adapted from the Joint British Diabetes Society for Inpatient Care
guidelines, with permission. [11]

([dagger]) Appropriate where no more than one meal missed in the
perioperative period.

([double dagger]) Check capillary blood glucose regularly while
fasting. The majority of international guidelines advise 1-or 2-
hourly measurements. Protocols with a 4-hourly measurement interval
carry a 10% hypoglycaemia risk. [18]

Table 4. Blood glucose management according to feeding status

Feeding status     Management options

Eating normally    Modification of usual therapy or basal-
                   bolus SC insulin with correction doses

Fasting            VRIII, modified Alberti's GIK, or basal
                   insulin only *

Tube enteral       VRIII, modified Alberti's GIK, or basal
feeding            insulin only *

Total              VRIII, modified Alberti's GIK, or basal
parenteral         insulin only *
feeding

SC = subcutaneous; VRIII = variable rate intravenous insulin infusion;
GIK = glucose-insulin-potassium infusion.

* It is best to avoid short-or rapid-acting insulin, as there is an
increased risk of hypoglycaemia However, small correction

Fig. 1. Basal-bolus insulin regimen. [16,25,26] (TDD = total daily
dose; CBG = capillary blood glucose; SC = subcutaneous.)

Three components

* Basal--once daily intermediate- or long-acting insulin

* Bolus--dosing at meal times with short- or rapid-acting insulin

* Correction--additional dosing at meal times with short-or rapid-
acting insulin to achieve or maintain the desired individualised
glycaemic target

For patients already on insulin, start with the patient's usual TDD

For insulin-naive patients, start with a TDD of 0.2--0.3 U/kg/day

[down arrow]

Give 50% of the TDD as basal insulin
Give 50% of the TDD as bolus doses (divide into 3 equal doses and give
before each meal)

[down arrow]

Give correction doses (added to the already prescribed insulin doses)
according to the following dosing scale:

                             Insulin correction dose, U

               Level 1                             Level 3
               (insulin                            (insulin
CBG, mmol/L    sensitive,        Level 2 (usual    resistant, TDD
               incl. fasting)    patient)          >80 U)

10.1-12.0      2                 4                 6
12.1-14.0      3                 6                 9
14.1-16.0      4                 8                 12
16.1-20.0      5                 10                15
>20.0          6                 12                18

To prevent insulin stacking, allow at least 4 hours between SC doses
of insulin Two-hourly dosing is acceptable intraoperatively

Reduce the basal doses to 80% of the usual dose on the night before
and the morning of surgery

Omit prandial dosing while fasting

Provide hypoglycaemia management instructions wherever insulin is
prescribed

Fig. 2. Variable rate intravenous insulin infusion regimen. [21,22]
(CBG = capillary blood glucose; IV = intravenous; TDD = total daily
dose; VRIII = variable rate intravenous insulin infusion; SC =
subcutaneous; DKA = diabetic ketoacidosis.)

Use a dedicated IV access site and infusion set with an antireflux
valve for glucose management

Add 50 U of regular short-acting insulin to 50 mL 0.9% NaCl
(1 mL = 1 U)

Administer with a syringe driver connected to a port close to the
dedicated IV cannula

Run dextrose/containing maintenance solution at 25 mL/kg/day (20//30
mL/kg/h range)

Monitor serum [Na.sup.+] and [K.sup.+] daily

Measure CBG hourly while the patient is under the influence of
anaesthesia; 2-hourly if normoglycaemic, awake, attended, and not
confused

               Insulin rates, mL/h

               Level 1                               Level 3
CBG, mmol/L    (insulin                              (insulin
               sensitive,         Level 2 (usual     resistant, TDD
               incl. fasting)     patient)           >80 U)

<4.0           Reduce VRIII to 0.2/0.5 mL/h (stop VRIII if SC basal
               insulin continued)
               Administer 20 g dextrose IV
               Repeat CBG in 15 min

4.1-6.0        Reduce VRIII to 0.2/0.5 mL/h (stop VRIII if SC basal
               insulin continued)
               Consider administration of 10 g dextrose IV to prevent
               CBG decreasing to <4.0 mmol/L
               Repeat CBG in 15 min

6.1-8.0        0.5                1                  2
8.1-12.0       1                  2                  4
12.1-16.0      2                  4                  6
16.1-20.0      3                  5                  7
20.1-24.0      4                  6                  8
>24.1          6                  8                  10

               Seek specialist advice

Target CBG range 6.0-12.0 mmol/L. CBG up to 12.0 mmol/L is acceptable
for a short period

Only increase VRIII if CBG remains high after 3 hours and is
decreasing by <3 mmol/L/h

There is a risk of DKA when discontinuing a VRIII, as it creates a
state of acute insulin withdrawal

Continue SC basal insulin while using a VRIII or administer SC basal
insulin 30 min before discontinuing a VRIII

Fig. 3. Management of perioperative hypoglycaemia. (CBG = capillary
blood glucose; DM = diabetes mellitus; IV = intravenous.)

Provide the diagnostic criteria and management of hypoglycaemia with
every in-patient diabetes prescription

A low CBG must be interpreted in the context of the patient's feeding
status and symptomatology

Decide whether the patient is at risk of hypoglycaemia unawareness.
These include the frail, patients on beta-blockers, with long-
standing DM, and those on medications with sedative effects. All such
patients, including those under the influence of anaesthesia, should
automatically be treated as symptomatic

CBG,        Without symptoms and          With symptoms or signs of
mmol/L      signs of hypoglycaemia        hypoglycaemia

            Normal diet    Fasting        Normal diet     Fasting

<4.0        Provide a      Give 10 g      Give 20 g       Give 20 g
            snack and      dextrose IV    dextrose IV     dextrose IV
            repeat the     and repeat     and repeat      and repeat
            CBG in 15-     the CBG in     CBG in 15 min   CBG in 15
            30 min         15-30 min      Seek urgent     min Seek
                                          help if no      urgent help
                                          response to     if no
                                          treatment       response to
                                                          treatment

4.0-6.0     Increase       Repeat CBG     Provide a       Give 10 g
            monitoring     within 30      snack and       dextrose IV
            frequency      min If         repeat CBG in   and repeat
                           persistent,    15--30 min      CBG in 15
                           give 10 g                      min Seek
                           dextrose IV                    urgent help
                           and increase                   if no
                           monitoring                     response to
                           frequency                      treatment
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Article Details
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Author:Biesman-Simons, L.du ToiT; Levy, N.; Dave, J.A.
Publication:SAMJ South African Medical Journal
Article Type:Report
Geographic Code:6SOUT
Date:May 1, 2018
Words:5310
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