|Year : 2018 | Volume
| Issue : 2 | Page : 17-26
Is it time to rethink about protocols for managing intraoperative serum potassium and blood glucose levels during off-pump coronary artery bypass surgery?
Kapil Gupta1, Pankaj Devi Dayal2, Shyam Bhandari3, Amitabh Kumar4, Carla Todaro5, Anoop R Gogia1, Poonam Malhotra6
1 Department of Anesthesia, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
2 Department of Anesthesia, Neuroscience Clinical and Research Center, Patliputra, Patna, Bihar, India
3 Department of Anesthesia, Dr Rajendra Prasad Medical College, Kangra, Himachal Pradesh, India
4 Department of Anesthesia, Orchid Hospital, Janakpuri, New Delhi, India
5 Department of Anesthesia, London Health Science Center, Schulich Western University, London, ON, Canada
6 Department of Cardiac Anesthesia, All India Institute of Medical Sciences, New Delhi, India
|Date of Submission||04-Jul-2018|
|Date of Acceptance||06-Sep-2018|
|Date of Web Publication||25-Oct-2018|
Dr. Kapil Gupta
Department of Anesthesia, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, 110029
Source of Support: None, Conflict of Interest: None
Background A low perioperative serum potassium level (<4 mEq/l) and high blood glucose level (>200 mg/dl) during cardiac surgery is a preventable cause of high morbidity and mortality. In this study, we measured the changes in intraoperative levels of serum potassium and blood glucose in adult patients undergoing elective off-pump coronary artery bypass (OPCAB) surgery, while administering insulin intraoperatively as per the present guidelines.
Patients and methods Thirty-six adults, aged 18–65 years, undergoing elective OPCAB surgery were enrolled in this study. Arterial blood gas analysis was performed at predetermined intraoperative time points to measure serum potassium and blood glucose levels as primary variables. Base excess, pH, and HCO3− were recorded as secondary variables. Insulin infusion was started according to the sliding scale, whenever blood glucose was more than 180 mg/dl. Intravenous potassium was supplemented, when serum potassium was less than 4 mEq/l. Quantitative variables were compared with baseline using paired t test and repeated measure analysis of variance was used for comparison across follow up.
Results Potassium chloride had to be continuously administered intravenous to maintain serum potassium levels more than 4 mEq/l throughout OPCAB surgery. There was a highly significant (P<0.001) increase in the intraoperative blood glucose level compared with the baseline throughout the OPCAB surgery.
Conclusion Patients are prone to hypokalemia and hyperglycemia during OPCAB surgery, despite following the current guidelines. More studies are needed to formulate a better insulin infusion protocol for maintaining normoglycemia and guidelines need to be formulated for continuous intraoperative potassium infusion during OPCAB surgery.
Keywords: blood glucose, hyperglycemia, hypokalemia, off-pump coronary artery bypass surgery, serum potassium
|How to cite this article:|
Gupta K, Dayal PD, Bhandari S, Kumar A, Todaro C, Gogia AR, Malhotra P. Is it time to rethink about protocols for managing intraoperative serum potassium and blood glucose levels during off-pump coronary artery bypass surgery?. Egypt J Cardiothorac Anesth 2018;12:17-26
|How to cite this URL:|
Gupta K, Dayal PD, Bhandari S, Kumar A, Todaro C, Gogia AR, Malhotra P. Is it time to rethink about protocols for managing intraoperative serum potassium and blood glucose levels during off-pump coronary artery bypass surgery?. Egypt J Cardiothorac Anesth [serial online] 2018 [cited 2019 Jun 18];12:17-26. Available from: http://www.ejca.eg.net/text.asp?2018/12/2/17/244161
| Introduction|| |
A high perioperative blood glucose level (>200 mg/dl) during cardiac surgery is associated with increased risk of postoperative infection, myocardial injury, left ventricular failure, cerebrovascular accidents, cognitive dysfunction, prolonged postoperative ventilation, prolonged length of hospital stay, and postoperative mortality ,,. Morbidity, hospital length of stay, inotropic support, and 5 years survival is attenuated by better control of blood glucose levels ,,. Intraoperative insulin infusion has not been found to effectively control the blood glucose levels in 18% of the cases despite following the current guidelines .
There are many studies reporting a perioperative increase in the blood glucose level during on-pump coronary artery bypass grafting (CABG) surgeries ,, mainly because of the high stress related to the use of cardiopulmonary bypass (CPB). They blamed the change in the internal environment due to CPB to be responsible for hyperglycemia . Serum potassium level less than 3.5 mEq/l is associated with an increased incidence of perioperative arrhythmias in cardiac surgery patients .
There is no study till date reporting the changes in blood glucose and serum potassium levels during off-pump coronary artery bypass (OPCAB) surgeries, without the use of CPB. The primary objective of this study was to measure the changes in the intraoperative serum potassium and blood glucose levels, while administering insulin infusion intraoperatively during OPCAB surgeries, as per current guidelines. We hypothesized that serum potassium levels decreased and blood glucose levels increased intraoperatively during OPCAB surgery despite insulin infusion.
| Patients and methods|| |
After obtaining clearance from the institutional ethical committee (VMMC/SJH/16/1786/12) and written informed consent from the patients, 36 adults of either sex undergoing elective OPCAB surgery were enrolled in this study. The study was conducted over a year from October 2016 to September 2017.
Inclusion and exclusion criteria
All adult patients (18–65 years) of either sex, undergoing elective OPCAB surgery were included in this study. Patients with hepatic dysfunction (abnormal liver function test like aspartate transaminase, alanine aminotransferase, bilirubin)/renal dysfunction (creatinine clearance >140 ml/min for males and >130 ml/min for females)/electrolyte abnormality or diabetes mellitus were excluded.
The preanesthetic assessment of all the patients was performed and the comorbidities/laboratory abnormalities were optimized. They were fasted for 8 h preoperatively. In the operating room, monitors [non-invasive blood pressure (NIBP], SpO2, ECG) were attached to the patient. Baseline parameters like age, sex, height, weight, diagnosis, and grafts to be performed were recorded and an 18 G intravenous cannula was secured in hand. Injection Midazolam 0.5 mg was administered intravenous and left radial artery was cannulated (under local anesthesia) for continuous arterial blood pressure monitoring.
Anesthesia was induced using Midazolam (0.03–0.05 mg/kg)/Fentanyl (5–7 μg/kg)/oxygen/air/propofol (1–2 mg/kg) and Vecuronium (0.1 mg/kg) administered intravenously. The endotracheal intubation was performed and the tube was secured. After induction, central venous pressure (CVP) line and pulmonary artery catheter were inserted in the right internal jugular vein. Anesthesia was maintained using O2/air/isoflurane and increments of Vecuronium and Morphine were administered intravenous. The depth of anesthesia was maintained using the bispectral index of 40–60. The patient was ventilated using the following settings [volume control mode; tidal volume (TV), 6–8 ml/kg; FiO2, 0.5; post end-expiratory pressure (PEEP), 5 cmH2O], to maintain ETCO2 33–37 cmH2O.
Arterial blood gas analysis was performed at predetermined intraoperative time intervals, to measure the levels of serum potassium and blood glucose as the primary variables. Base excess, pH and HCO3− levels were recorded as secondary variables. The time intervals were immediately after arterial cannulation (T0), before grafting (T1); thereafter, every 30 min, at 30 min (T2), 60 min (T3), 90 min (T4), 120 min (T5), end of graft (T6), and end of the surgery (T7). Average time points of ‘end of graft’ (T6) and ‘end of surgery’ (T7) were 3 and 4 h, respectively.
Insulin infusion was started according to the sliding scale, whenever blood glucose was more than 180 mg/dl (Appendix 1). The insulin infusion was titrated according to the sliding scale (Safdarjung Hospital protocol), every time the blood glucose level was monitored at the predecided time point. The aim was to maintain the blood glucose level 120–180 mg/dl, as per society of thoracic surgeon guidelines . The hospital insulin sliding scale protocol was developed according to the consensus evidence-based guidelines for patients undergoing CABG to have a better intraoperative control of blood glucose level (Appendix 1) ,.
Hypoglycemia was defined as blood glucose levels less than 80 mg/dl. In case of any hypoglycemic event, the protocol was to discontinue insulin infusion, administer 100 ml of 5% Dextrose intravenous, and recheck the blood glucose level.
The potassium levels were measured at predetermined time points. Whenever the serum potassium level was less than 4 mEq/l, potassium chloride infusion was started intravenously via the central line. It was started at 10 mEq/h when potassium level was 3.5–4 mEq/l and infusion was increased to 20 mEq/h when potassium level was less than 3.5 mEq/l (hospital protocol). The infusion of potassium chloride was stopped whenever potassium level was more than 5 mEq/l.
Heparin (1–1.5 mg/kg) was administered to maintain the activated clotting time (ACT) of 250–300 for grafting. Infusions of Dopamine/Dobutamine/Norepinephrine/Epinephrine and Nitroglycerine were administered intravenously (if required), as per the standard institute protocol. The hemodynamic variables of the patient were maintained within the normal limits. At the end of the grafting, Heparin was reversed with Protamine. After completion of the surgery, the patient was shifted to Cardiac ICU for intensive monitoring and elective ventilation. Postoperatively, the patient was extubated after 6 h.
Sample size calculation
The sample size of our study was calculated on the basis of the pilot study, in which blood glucose levels were significantly correlated with each other (P<0.0001) and there was a nonsignificant correlation of serum potassium levels with each other. Cohen’s effect size was used to calculate the sample size of one sample with a continuous outcome variable. To detect medium scale effect size (0.5 or 50%), the minimum required sample size with 80% power of the study and two-sided alpha of 5% was 32 patients. Allowing 10% patients drop out, it was decided to have a total sample size of 36 patients. The formula used was:
where Zα is the value of Z at the two-sided alpha error of 5% and Zβ is the value of Z at the power of 80%, and ES is effect size.
Categorical variables were presented in number and percentageand continuous variables were presented as mean±SD. Normality of data were tested by the Kolmogorov–Smirnov test. If the normality was rejected then nonparametric test was used. Quantitative variables were compared with the baseline using paired t test and repeated measure analysis of variance was used for comparison across follow up, and the Pearson correlation coefficient was used for correlation of insulin administered or blood glucose levels with potassium administration at different time points. A P value of less than 0.05 was considered statistically significant. The data was entered in MS Excel spreadsheet and analysis was done using SPSS, version 21, Microsoft Excel version 16 and SPSS 20 (IBM, Armonk, NY, United States of America).
Type of study
Cross-sectional time series analysis.
| Results|| |
The demographic profile of our patients is shown in [Table 1]. There was a highly significant (<0.001) increase in intraoperative blood glucose levels compared to the baseline throughout the OPCAB surgery ([Figure 1]). The mean blood glucose levels remained greater than 200 mg/dl from 30 min of starting the graft until the end of the grafting. The insulin-infused intravenous with time during OPCAB surgery is shown in [Table 2]. Within 60 min of starting the grafting, 13 (36%) patients were on insulin infusion. At least seven (20%) patients were on insulin infusion throughout the grafting process.
|Figure 1 Changes in intraoperative blood glucose levels (mean±SD, mg/dl). Repeated measure ANOVA was used for analysis (P<0.001). ANOVA, analysis of variance.|
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|Table 2 Insulin infusion rate (IU/ml) at different time points during off-pump coronary artery bypass surgery|
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The mean intraoperative serum potassium levels were greater than 4 mEq/l at different time points as we continuously replaced potassium (potassium infusion) throughout the surgery. The serum potassium levels were not significantly different from the baseline and from each other, with increased duration of the surgery (P=0.86, [Figure 2]). The potassium chloride administered intravenous over different time points during OPCAB surgery is shown in [Table 3]. Throughout the surgery, a mean of 6 ml/h of potassium chloride was administered at every time point, to maintain serum potassium more than 4 mEq/l ([Table 3]). In 16 (41%) patients, 7.50±4.08 ml/h (mean±SD) of potassium chloride was administered 30 min after starting the grafting. The intraoperative changes in HCO3−, base excess, and pH during OPCAB surgery were not significantly different from the baseline, as the surgery progressed ([Table 4]). There was no significant correlation between blood glucose levels and the amount of potassium administered to keep potassium level above 4, except at the end of grafting process (P=0.03) ([Figure 3]). There was no significant correlation between the amount of insulin required to control blood glucose levels and the amount of potassium administered to keep potassium level above 4 at different time points ([Figure 4]).
|Figure 2 Changes in intraoperative serum potassium levels (mean±SD, mEq/l). Repeated measure ANOVA was used for analysis (P=0.86). ANOVA, analysis of variance.|
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|Table 3 Potassium supplementation at different time points during off-pump coronary artery bypass surgery|
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|Table 4 Base excess, pH, and bicarbonate (HCO3−) values at different time points during off-pump coronary artery bypass surgery. Repeated measure analysis of variance was used for analysis|
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|Figure 3 Correlation between blood glucose levels and the amount of potassium administered intraoperatively. Pearson correlation coefficient was used for correlation.|
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|Figure 4 Correlation between the amount of insulin and potassium administered intraoperatively. Pearson correlation coefficient was used for correlation.|
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| Discussion|| |
This is the first study reporting the intraoperative changes in serum potassium and blood glucose levels during OPCAB surgery, whereby the patients were being administered insulin as per the current guidelines. This study highlighted that intraoperative blood glucose levels increased significantly (P<0.001) over time as the duration of surgery progressed, despite insulin infusion and potassium chloride had to be continuously administered intravenously to maintain serum potassium levels greater than 4 mEq/l throughout the OPCAB surgery. This study also highlights that the grafting process is associated with hyperglycemia, as reflected by blood glucose more than 200 mg/dl throughout the grafting process. This study also emphasizes the need to develop a protocol for continuous infusion of potassium during OPCAB surgery.
This is an important manuscript as it highlights the deficiency in managing serum potassium and blood glucose levels during OPCAB surgery as per the current guidelines. We administered insulin as per our hospital protocol, which was developed according to the current guidelines. Our study highlights that dosage of insulin according to the current guidelines for maintaining blood glucose levels between 120 and 180 mg/dl during OPCAB surgery is unable to maintain the targeted levels, as blood glucose levels were greater than 200 mg/dl during most of the grafting process. At present, there is no uniform insulin infusion protocol for intraoperative control of blood glucose levels between 120 and 180 mg/dl. Different institutes across the world have developed their own insulin infusion protocols ,.
The increase in blood glucose levels may be due to the release of stress hormones like cortisol, vasopressin, and catecholamines in response to the stress of OPCAB surgery and anesthesia . These stress hormones inhibit glucose utilization by the peripheral tissues. The maximum increase in blood glucose levels (>200 mg/dl) was seen during the grafting of coronary vessels ([Figure 1]). This may be the most stressful period of OPCAB surgery. In our study, the use of intravenous infusion of dobutamine/dopamine/norepinephrine/epinephrine intraoperatively would have further contributed to hyperglycemia. Catecholamines stimulate the production of endogenous glucose, which counter the action of insulin and inhibit the release of insulin by stimulating pancreatic α-receptors . Other contributing factor in our study may be morphine-induced opening of pancreatic K+-ATP channels, leading to the inhibition of insulin release . We excluded diabetic patients in our study to have more uniformity of results, as diabetic patients may have a different glycemic response, due to their underlying disease and the use of hypoglycemic medications.
There is a gradual increase in intraoperative blood glucose level in both diabetic and nondiabetic patients undergoing on-pump CABG surgeries with increased duration of surgery . Prasad et al.  reported that 70% of nondiabetic patients have intraoperative blood glucose levels more than 200 mg/dl during on-pump CABG surgeries. Hyperglycemia leads to an increase in fatty acid levels, which accentuates the myocardial oxygen demand and decreases the myocardial uptake of glucose . This attenuates the production of ATP, causing dysfunction of cellular membranes, leading to cardiac arrhythmias and ventricular function abnormalities . Hyperglycemia accentuates the reperfusion injuries and activates protein kinase C, stimulating the production of reactive oxygen species, which cause endothelial dysfunction . Protein kinase C also activates the production of endothelin-1, which causes platelet aggregation, vascular inflammation, and vasoconstriction . Hence, hyperglycemia is detrimental for patients undergoing the cardiac surgery. Recently, higher preoperative HbA1C levels have been associated with major adverse events and early saphenous vein graft failure after CABG ,.
Strict blood glucose control in patients undergoing myocardial revascularization decreases the rate of wound infection and duration of hospitalization . There was 30% decrease in mortality rate in patients after myocardial infarction, by maintaining blood glucose levels less than 200 mg/dl ,. There was a significant decrease in perioperative complications in patients without diabetes who underwent CABG with intensive control of blood glucose when compared with conservative treatment (34 vs. 55%, P=0.008) . Tight control of blood glucose in diabetic patients undergoing CABG decreases the requirement of inotropes, the incidence of arrhythmias, and duration of ventilation, with a higher 5 y survival rate . Patients without diabetes having high intraoperative blood glucose level more than 200 mg/dl have worse prognosis than the diabetic patients .
Practice guidelines of ‘The Society of Thoracic Surgeons’ advocate the use of insulin infusion to maintain blood sugar less than 180 mg/dl during the perioperative period . It is important to maintain blood glucose between 120 and 180 mg/dl (6.7–10.0 mmol/l), as the incidence of hypoglycemic episodes increase when blood glucose is targeted less than 120 mg/dl (strict control) ,. Sanjay et al.  reported that 60% of nondiabetic patients and 10% of diabetic patients, who underwent elective CABG with tight control of intraoperative blood glucose, were treated for postoperative hypoglycemia. Rujirojindakul et al.  reported that 23% of patients with intensive blood glucose control had intraoperative hypoglycemia. Desai et al.  concluded that control of blood glucose in a liberal range (120–180 mg/dl) after CABG had similar outcomes when compared with a strict range (90–120 mg/dl).
In our study, serum potassium levels were maintained within normal limits (>4 mEq/l) by continuous intraoperative administration of potassium chloride. We replaced potassium continuously to prevent hypokalemia (<4 mEq/l) as lower levels of serum potassium (<3.5 mEq/l) were associated with cardiac arrhythmia ,. The serum potassium levels would have decreased intraoperatively if we had not regularly replaced potassium. Administration of insulin in our study would have contributed to the decrease in the serum potassium levels, by moving potassium intracellularly from the extracellular compartment. Administration of thiazide diuretics and alkalosis also leads to decrease in potassium levels . In our study, diuretics or mannitol were not administered intraoperatively, and blood pH was maintained within the normal limits (7.35–7.45). But many of our patients were taking antihypertensive medications (including thiazide diuretics) preoperatively, which could have contributed to hypokalemia. At present, there are no guidelines for continuous replacement of potassium intraoperatively during OPCAB surgery. Hypokalemia during OPCAB is a preventable cause of high morbidity, and we need to develop intraoperative potassium replacement protocols to prevent hypokalemia during OPCAB surgery.
Potassium plays an important role in maintaining cellular polarization and transmission of electrical impulses through the myocardium . Hypokalemia leads to cellular hyperpolarization, increases the resting membrane potential, automaticity, and excitability . Hypokalemia predisposes to perioperative cardiac arrhythmias by altering electrophysiological properties of cardiac myocytes, increasing the duration of phase 3 depolarization, decreasing conduction velocity, and enhancing automaticity . The association between hypokalemia and arrhythmias is further accentuated in the presence of acute myocardial ischemia, with an increased incidence of ventricular tachycardia and fibrillation ,. Keskin and colleagues evaluated patients with ST elevation myocardial infarction and found that the lowest mortality rate was found in patients with serum potassium levels of 4–4.5 mEq/l. The mortality rate was higher when the serum potassium level was less than 3.5 mEq/l or greater than 5.0 mEq/l .The hypokalemia and hyperglycemia during OPCAB surgery are multifactorial, and no exact dose relationship could be established between insulin dosage administered and the level of hypokalemia achieved or the blood glucose levels and the amount of potassium administered at different time points. Recently, glucose–insulin–potassium infusion has been demonstrated to have a myocardial protective effect during CABG with better postoperative outcomes, demonstrated by decreased postcardiotomy ventricular dysfunction, decreased plasma troponin levels , and lower creatinine kinase-MB levels in the early postoperative period in glucose–insulin–potassium group .
There are some limitations in this study. The sample size of the study group was small. We did not measure serum insulin levels intraoperatively. We did not measure the biological indicators of stress response like cortisol and catecholamines to find any direct causative correlation of these hormones with increased glucose levels. In future, researchers can measure these biological indicators of stress response and correlate the impact of stress on hyperglycemia in OPCAB surgeries. We replaced potassium at regular intervals and did not allow potassium levels to decrease significantly, as we did not want any patient to have arrhythmia. Hence, we could not measure the true uncorrected serum potassium levels intraoperatively. We did not perform the long-term morbidity and mortality analyses related to hypokalemia and hyperglycemia.
| Conclusion|| |
This study highlights that intraoperative blood glucose level increases during OPCAB surgery, despite continuous administration of insulin as per the current guidelines. The current protocols available including standardized insulin infusions does not adequately control the glucose fluctuations during OPCAB surgery. In future, different insulin infusion dosages can be studied to maintain glucose level between 120 and 180 mg/dl intraoperatively. Continuous intraoperative infusion of potassium maintains potassium levels during OPCAB surgery. There is a need to investigate and formulate guidelines for continuous infusion of potassium intraoperatively during OPCAB surgery.
Financial support: Department of Cardiac Anesthesia, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi 110029, India.
Work was done in Department of Cardiac Anesthesia, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi 110029, India.
Clinical Registry: Australian Registry (ACTRN 12616001395426).
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4]