THE EFFECT OF SUCCINYL CHOLINE ON SERUM POTASSIUM LEVELS IN PATIENTS WITH INTRA-ABDOMINAL INFECTION

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1 SOODAN, Indian J. Anaesth. KAUL, SINGH, 2003; 47 BAJWA (2) : : SUCCINYL CHOLINE AND SERUM K 105 THE EFFECT OF SUCCINYL CHOLINE ON SERUM POTASSIUM LEVELS IN PATIENTS WITH INTRA-ABDOMINAL INFECTION SUMMARY Dr. Anjali Soodan * Dr. T. K. Kaul * Dr. Avtar Singh * Dr. S. Bajwa * The serum potassium (K + ) levels and serum ph levels were studied following injection of Succinyl choline (1.5 mg per kg. body weight) in 50 patients who were divided into two groups, a study group of twenty five patients with intra-abdominal infections and a control group of twenty five patients of routine abdominal surgery with no evidence of sepsis. The central venous blood samples for serum K + and ph were drawn preoperatively and at 1,3,5, and 10 minutes after induction and injection of Succinyl choline. On initial analysis, there were no significant changes in serum K + levels in both groups. On further analysis, a subgroup of 11 patients with intrabdominal infections with a duration of illness> 7 days (mean duration days) showed significant rise in serum K + levels (³ 0.5 meq/l above baseline) achieving maximum levels at 5 minutes and 10 minutes compared to pre induction levels (p value < 0.05). The type and severity of infection did not have any significant effect on serum potassium changes. Serum ph also did not reveal any significant effect on the serum K + levels. Keywords : Succinyl choline, Hyperkalemia, Infections, Intra-abdominal sepsis. Introduction A physiological rise of serum potassium (K + ) up to 0.5 meql -1 has been observed in normal healthy subjects following Suxamethonium administration and has been attributed to muscle cell damage due to asynchronous depolarization. 1,2,3 Conditions especially susceptible to hyperkalemic response from suxamethonium administration are burns, 4 trauma, 5 nerve damage and neuromuscular disease, 6 closed head injury 7,8 and renal failure. 9 Several instances of cardiac arrests have been reported following suxamethonium 10 and this particular side effect came more into limelight in 1993 following a report of twenty cases of sudden hyperkalemic induced cardiac arrests with the use of suxamethonium in patients of undiagnosed myopathies. 11 In addition to above, there have been studies of suxamethonium induced hyperkalemia in patients with infections 12 especially with intra-abdominal sepsis. 3,14 It has been suggested that patients with intra-abdominal infections lasting longer than one week represent an additional category susceptible to suzamethonium induced hyperkalemia. 13 Intra-abdominal sepsis is commonly encountered in India 15 thus presenting need for emergency abdominal surgery. Suxamethonium is the drug of choice in rapid sequence induction in such cases. In view of earlier reports Correspond to : Dr. T. K. Kaul * Dept. of Anaesthesiology Dayanand Medical College & Hospitals Ludhiana, Punjab. of suxamethonium induced changes in these patients, it was considered worthwhile to study the effects of this drug on serum K + in patients with intra-abdominal infections undergoing exploratory surgery and compare the changes in patients undergoing routine surgery. The other variables affecting the serum K + levels like duration of illness, severity of illness, and type of infections were also studied. Material and methods The prospective study was carried out in Dayanand Medical College and Hospital on fifty adult patients of both sexes between years of age admitted for elective and emergency abdominal surgery after approval of hospital ethical committee. A written informed consent was obtained from all patients. The patients were divided into two groups of twenty five each comprising control group and study group. The control group consisted of ASA I and II patients posted for various elective abdominal surgeries without any evidence of intra-abdominal sepsis. The study group comprised of 25 patients-asa II, III and IV (E) with clinical diagnosis of intra-abdominal sepsis undergoing emergency abdominal surgery. The study group patients were further subdivided into two subgroups of 11 and 14 patients respectively based on duration of illness into patients with duration of illness less than 7 days (n=11) and duration of more than 7days during the course of study (n=14). The patients at risk of succinyl choline induced hyperkalemia like trauma, metabolic disease, dehydration and those receiving i.v. fluids containing potassium or

2 106 INDIAN JOURNAL OF ANAESTHESIA, APRIL 2003 receiving blood transfusion four hours prior to surgery were excluded from the study. A thorough preanaesthetic check up was done in all the patients prior to the surgery. Preoperative investigations including haemogram, renal function tests, random blood sugar, X-ray chest PA view and ECG were done in all the patients. The information was filled in a proforma designed especially for the study. All the patients were premedicated with injection atropine 0.3 mg and injection pentazocine 0.5mgkg -1 I.M. half an hour before induction and received either 0.9% normal saline or 5% Dextrose in 0.9% normal saline before surgery. Intraoperative monitoring included pulse oximetry, ECG lead II, heart rate (L & T Medical (Micromon make). NIBP (Dinamap Critikon TM 1846 sx) and CVP using a saline manometer. Intravenous access was achieved in dorsum of both hands using 18 G IV canula and a central venous access was obtained by inserting a 14 G Cavafix (B.Braum) through the right antecubital vein. The placement of catheter tip in superior vena cava was confirmed by portable X-ray taken in operating room soon after. A rapid sequence induction was done after preoxygenating with 100% oxygen for 3 minutes. Anaesthesia was induced with a sleep dose of 2.5% thiopentone, cricoid pressure was applied and endotracheal intubation was facilitated with succinyl choline 1.5mgkg -1. Anaesthesia was maintained with 0.5% halothane in oxygen (4 lmin -1 ) and nitrous oxide (6 lmin -1 ). Muscle relaxation was provided with pancuronium bromide (0.08 mgkg -1 ) and additional doses were given as required. All the patients wre ventilated mechanically using Medivent Servo At the end of the surgical procedure the effect of muscle relaxation was reversed with neostigmine 0.04 mgkg -1 and supplemented with glycopyrrolate 0.01 mgkg -1 IV. Trachea was extubated in all the cases. Sampling Two series of blood samples (2 ml each) were collected from central venous line after discarding 4 ml of blood before each sample-first series of samples were collected in plain syringes for estimation of serum K + and for second series the collection was done in heparinised syringes for estimation of ph. Samples were drawn in each group just before induction and at one, three, five and ten minutes after succinyl choline administration and labeled appropriately. The samples were immediately transported to the laboratory of biochemistry for analysis. The estimation of serum ph was done using H+ion selective electrode ( STAT profile IV ABG analyzer ) and serum K + estimation using sodium-potassium autoanalyzer ( Easy lyte plus ). In the study group, the peritoneal fluid was collected in sterile calibrated suction bottle from each case patient and analyzed for gram staining and aerobic culture for organism identification. The statistical analysis was done using paired t test for within group analysis and unpaired t for inter group analysis. The p values of < 0.001, < 0.01 and <0.05 were taken as significant. Analysis of Variance (ANOVA) was applied for detecting any intragroup variation in serum ph and serum potassium levels. Chi square test was used to compare serum potassium levels in control group, study group and study subgroups. A p value of <.05 was taken as significant. Results Patients Characteristics The mean age, weight and sex were comparable in two groups see table 1. In Study group (n=25) th clinical diagnoses were as follows: Perforation of small intestine 10 (40%). Perforation of large intestine 7 (28%), Uterine perforation with peritonitis 5(20%). Chronic cholecystitis with perforation 1 (4%) and Ruptured pyogenic liver abscess 2(8%). In Control Group (n=25), the diagnosis were as follows : Diagnostic laparotomy 12 (48%). Pyelolithotomy 3(12%), Cholecystectomy 4(16%). Cesarean Section 6(24%). The mean duration of illness in the study group was 9.57±12.33 days (3-60 days). There were 11 cases (44%) with duration of illness exceeding 7 days (subgroup- A) and 14 cases (54%) with duration of illness less than 7 days (subgroup-b). The pulse rate and respiratory rate were significantly higher in the study group preoperatively. The preoperative total leukocyte count was 7371±1008.2/mm 3 and in study group was 12681±3595.4/mm 3. The Preoperative TLC of the study group was significantly higher. The mean quantity of the peritoneal fluid drained from the abdomen was 1.138±0.774L (0.2-2 L). The fluid was serous in nature in 8 cases, purulent in 12 cases and faeculent in 5 cases. The peritoneal fluid showed leucocytosis and gram negative bacterial growth of Escherichia coli, Pseudomonas, Salmonella and Klebsiella on culture. The details of various clinical and haemodynamic parameters are described in table-1.

3 SOODAN, KAUL, SINGH, BAJWA : SUCCINYL CHOLINE AND SERUM K 107 Table - 1 : Demographic and clinical and Laboratory Parameters. S.No. Variable Control Group Study Group (mean ± S.D.) (n=25) (n+25) 1. Age in years 36.28± ± Sex (male:female) 12:13 13:12 3. Weight (kg) 42.23± ± Pulse rate per minute 79.54± ± Resp. Rate per minute 14.22± ± NIBP in mm Hg (Sys) 121.3± NIBP in mm Hg (Dia) ± ± Hemoglobin (gm per dl) ± ± Total leucocyte count 73.71± ± (per mm3) * 10. Urea (mg per dl) 34.2± ± Creatinic (mg per dl) 1.14± ± Blood sugar (mg per dl) 111.3± ±47.66 Note:- * = p<0.01 (Student s test applied) Changes in serum ph The mean base line ph in the study group was 7.26±.004 while in the control group it was 7.37± The changes in serum ph levels at various intervals after succinyl choline were not significant as compared to the pre induction ph levels in both the groups see table-2. Table 2 : Serum ph in study group and in control group. S. No. Time Interval after Serum ph (Mean±SD) Study (meq/l) Control (meq/l) 1. Baseline 7.26± ± min 7.28± ± min 7.25± ± min 7.27± ± min 7.28± ±0.456 P = non significant (Student s test ) Changes in serum K + Serum potassium levels were tested immediately before suxamethonium injection and then serially at one, three, five and ten minutes in both the groups. The mean baseline value of serum K + in study group was 3.636±0.36mEqL -1. The range of change in serum K + at one minute, 3 minutes, 5 minutes and ten minutes was 0.6 to 2.1 meql -1,-0.6 to 4.39 meql -1, -0.1 to 3.09 meql -1 and -0.1 to 1.0 meql -1 respectively. The maximum increase in serum K + was seen at three and five minutes intervals. In the study group, 11 cases (44%) had an increase of more than 0.5 meql -1 than in serum K + levels from baseline value (greater than the usual physiological rise in serum K + following suxamethonium). Another group of six cases (24%) actually showed a decrease in serum K + from the base line value while in rest of the cases (36%) the rise was less than 0.5mEqL -1. The changes are described in table 3. Table - 3 : Serum Potassium levels (meq/l) in study Group. S. No. Time Interval after Serum ± Study Group Mean S.D. 1. Baseline 36.36± min 3.881± min 3.985± min 3.984± min 3.966±0.47 P = non significant (s.no. 2,3,4,5 were compared with value at s.no.1) Two way analysis of variance (ANOVA) = non significant The base line serum K + levels in control group was 4.566±0.58 meql -1 and the v`````alues obtained at subsequent intervals are as given in table 4. The levels showed a maximum changes at 5 and 10 minutes intervals. There were 7 cases in the control group which showed a decrease in serum K + levels from base line while in the rest of the cases the increase was less than 0.5 meql -1 at all intervals following Suxamethonium. Table - 4 : Serum Potassium levels (meq/l) in control group. S. No. Time Interval after Serum±Study Group Mean S.D. 1. Baseline 4.566± min 4.705± min 4.782± min 4.793± min 4.852±0.491 P = non significant (s.no. 2,3,4,5 were compared with value at s.no. 1)Two way analysis of variance (ANOVA) The changes in serum K + levels from baseline after suxamethonium did not reveal any significant differences in both the groups.

4 108 INDIAN JOURNAL OF ANAESTHESIA, APRIL 2003 The values thus obtained were analysed using two way ANOVA to detect any significant change from the baseline potassium levels in both the groups in serum (K + ) levels similarly analysed before and after succinyl choline did not reveal any significant differences in both study and control groups. We studied the characteristics of the patients of the study group (designated as subgroup A) where the duration of illness was more than 7 days and compared it with the rest of the subjects from the study group with duration of illness less than 7 days (subgroup B). Subgroup A has the following cases: perforation of Small Intestine 4 cases, Post MTP peritonitis 3 cases perforation of large Intestine 1 case, chronic cholecystitis with perforation 1 case and ruptured pyogenic liver abscess 2 cases. In subgroup B the cases were as follows: perforation small Intestine 6 cases, perforation of large Intestine cases and uterine perforation 2 cases. The haemodynamic and laboratory parameters are described in Table- 5. One remarkable difference in both these subgroups is the duration of illness (p<05) and this justified the subgrouping on this very basis. Table 5 : Characteristics of the two subgroups of Study group. Parameters Subgroup with duration Subgroup with duration >7 days n=11 >7 days n=14 Age (Year) 34.88(5.08) 37.00(14.85) Blood Pressure (24.96) (25.64) Systolic (mmhg) Diastolic (mmhg) 80.88(10.63) 77.72(27.91) Pulse (Per minute) (21.80) (15.43) Respiration rate/ min 23.00(4.89) 23.88(6.4) Temperature ( 0 F) (1.509) 99.90(1.136) Total leucocyte count ( )/mm3 ( )mm3 Amount of pus 1.2 liters (0.545) 0.91 liters(0.748) Mean duration of (12.79) 4.18*(1.16) illness(days) SD is given in bracket along with mean. *p<.01, p=non significant in all other variables. The variation in serum potassium levels in two subgroups are described as in table-6. It clearly shows than mean increase in serum K + levels from baseline is statistically significant in subgroup A (patient with prolonged duration of illness) as compared to the changes in subgroup B. (ANOVA) Table 6 : Serum Potassium changes after administration in study group sub groups. S/N. Time Interval Subgroup A Subgroup B after Serum K + erum K + Mean Mean Mean Mean (S.D.) change (S.D.) change 1. Base Line 3.628± ± One minute 4.252± (0.56) 3.76± (0.85) 3. Three minute 4.613± ±(1.92) 3.47± (0.23) 4. Five minute 4.54±0.82* 0.91(0.85) 3.63± (0.06) 5. Ten minute 4.34±0.41* 0.71 (0.20) 3.69± (0.17) Note :- * = p < 0.01 Discussion It is well known that Succinylcholine cause potentially catastrophic hyperkalemia in certain subsets of patients, especially those with damaged, muscle mass 10 burns, 5 trauma, 7,8 nerve damage 6 and as a result certain conditions like myopathies have been clearly accepted as categories susceptible to such an effect. There have been attempts to document such an effect in patients with intra-abdominal sepsis, 13,14 but the evidence that patients with intra-abdominal infections are susceptible to Suxamethonium induced hyperkalemia is not strong enough. In the present study an attempt was made to study the effects of on serum K + levels in patients with intra-abdominal infections as compared to similar effects in patients of control group undergoing routine abdominal surgery with no evidence of infection. In control group, there were no statistically significant variations in serum K + after Suxamethonium administration as compared to baseline levels. The mean serum K + levels at 5 and 10 minutes were 4.79 meql -1 and 4.85 meql -1 (The range of mean rise being 0.16 meql -1 to 0.29 meql -1 at these time intervals). A rise exceeding 0.5 meql -1 has been reported by researchers. 1,2,3 This rise has been termed physiological due to asynchronous muscle contraction following Suxamethonium. 3 In patient with intra-abdominal sepsis, these was slight rise in serum K + level. The maximum rise was seen at 5 minutes interval (3.985 meql -1 from meql -1 ) This change was statistically insignificant using two way ANOVA. Only eleven (44%) of total twentyfive subjects showed an increase of 0.5 meql -1 or

5 SOODAN, KAUL, SINGH, BAJWA : SUCCINYL CHOLINE AND SERUM K 109 above and one case showed the greatest rise, that is 4.3 meql -1 from baseline. Thus this study failed to show any significant rise of serum K + after Suxamethonium in patients with intra abdominal sepsis. A finding contrary to previous literature reports. 13,14 One factor likely to affect the serum K + changes could have been serum ph. Acidosis increases and alkalosis decreases the serum K + concentration. The variations in serum ph in this study were not of magnitude so as to affect the change in serum K + (An average 0.1 unit change in extracellular ph produces an inverse change of 0.6 meql -1 in serum K + concentration. 16 The overall change in serum ph in our study as well as control group never exceeded >0.02 units. Moreover the effect of acidosis on induced hyperkalemia is not linear and probably acidosis is not related to an increase in serum K + concentration. 17,18 However in the present study, a subgroup of patients suffering from intra-abdominal sepsis with duration of illness more than 7 days was showing a significant rise of serum K + at 5 and 10 minute interval (p<0.1). All the patients (n=11) showed a rise of 0.5 meql -1 or above and maximal rise of 4.3 meql -1 was shown by a patient with duration of illness around 60 days. The mean rise of serum K + was far greater than compared to subgroup (n=14) with duration of illness less than 7 days though both the subgroups were comparable on various parameters of severity like, total leucocyte count (TLC) and amount of pus. Moreover, the correlation between duration of illness and mean rise of serum K + in this subgroup was significant statistically (p<0.01), wherever the correlation between mean rise of serum K + and TLC and amount of pus was not significant. It is worth while to consider these findings in light of the following findings from the previous studies: a) Previous studies have shown that a substantial rise of serum K + is not shown by all the patient having intra abdominal sepsis. In fact, significant rise of serum K + after suxamethonium have been shown only by a portion of study group patients in previous studies. 12,13,14 In study by Kohlschutter et al 13 three patients showed a rise of meql -1. In Khan etal 12 study, 20% patients showed a rise of meql -1. b) Patients who have shown a substantial rise of serum K + after suxamethonium have one feature in common, i.e., the duration of illness usually exceeded markedly the duration of illness in other patients. In Kohlschutter study, 13 four patients showing marked rise in serum K + after Suxamethonium had been suffering from abdominal sepsis for 2 weeks or more while Khan et al 12 showed maximal rise in serum K + occurred in patients with infection of 8-21 days duration. So it seems that factors related to severity of infection like total leucocyte count and amount of pus do not seem to be important for suxamethonium induced hyperkalemia in patients with intra-abdominal sepsis. Only factor consistently related to significant rise of serum K + after suxamethonium in present study as well as in previous studies is duration of infection. It has been speculated that pathophysiological mechanisms related to bed rest and immobililzation may operate in these cases of intra abdominal sepsis. In these patients, bed rest many lead to relative immobilization of several muscles and administration of Suxamethonium may result in significant potassium rise in such cases. 3,19 Immobilization and bed rest have been important in hyperkalemic responses after suxamethonium in intensive care patients. 20,21,22,23 Immobilization has been postulated to be responsible for rise of 5.7 meql -1 in serum K + which was adequate to cause cardiac arrest in a patient. 20 Moreover such response may not be seen during challenges in the early period of bed rest. 24 This can explain the significant rise of serum K + after suxamethonium in a subgroup of patients with intra-abdominal sepsis in the present study. Researchers have pointed out that immobilization is comparable but lesser in magnitude to denervation syndromes in that there is less muscle atrophy, enlargement of acetylcholine sensitive areas, proliferation of acetyl choline receptors, decreased choline esterase activity and sprouting of terminal branches. 3,19 This may explain the degree of rise of serum K + following suxamethonium in the present study as the mean rise was far less than what may be termed as potentially lethal rise of serum K +. Hence it is quite possible that prolonged confinement to bed or immobilisation rather than infection may be more important factor for assessing the risk for hyperkalemia following use of suxamethonium in patients with intra-abdominal sepsis. Based on these findings it can be concluded that rise in serum K + following suxamethonium use in patients with intra-abdominal sepsis is rarely hazardous and at present these is no conclusive evidence to label these patients as an additional category susceptible to potentially lethal rise of serum K + following use of suxamethonium.

6 110 INDIAN JOURNAL OF ANAESTHESIA, APRIL 2003 References 1. Paton WDM. Mode of action of neuromuscular blocking agents. Br J Anaesth 1956; 2: Paton WDM. The effects of muscle relaxants other than muscular relaxation. Anesthesiology 1959; 20: Fung DL, White DA, Jones BJ, Gronert GA. The onset of disease related potassium efflux to. Anesthesiology 1991; 73: Allan CM. Cullen WG. Gillies DMM: Ventricular fibrillation in a burned boy. Curr. Med. Assoc. 1961; 85: Birch AA, Mitchell GD. Playford GA, Long CA. Changes in serum potassium in response to succinyl choline following trauma. JAMA 1969; 210: Cooperman LH : Succinylcholine induced hyperkalemia in neuromuscular diseases. JAMA: 1970; 213: Stevenson PH. Birch AA. Succinylcholine induced hyperkalemia in a patient with a closed head injury. Anesthesiology 1979; 51: Frankville DD. Drummond JC. Hyperkalemia after administration in a patient with closed head injury without paresis. Anesthesiology 1987; 67: Powell R, Miller RD. The effect of repeated doses of on serum K + in patients with renal failure. Anesth Analg. 1976; 54: Martyn JAJ; White DA: Gronert GA, Jaffa SR and Ward JM. Up and down regulation of skeletal Muscle Acetyl Choline Receptors Effects on Neuro muscular blockers. Anesthesiology 1992; 76: Rosenberg H, Gronert G, Intractable cardiac arrest in children given succinyl choline. Anesthesiology 1992; 77: Khan TZ & Khan MR; Changes in serum Potassium following in patients with infections. Anesth Analg 1983; 62: Kohlschutter BH, Roth F. Suxamethonium induced hyperkalemia in patients with severe intra abdominal infections. Br J Anaesth 1976; 48: Bhukal B, Batra YK, Kumar AR and Sarkar A, Serum potassium levels following. Suxamethonium administration in septic peritonitis patients. Indian J. Med Res (B) 94 June 1991; PP Kumar PS. Et al. Prognosis in intraabdominal sepsis. Indian J. Gastroentrol. 1995; Jan: 14(1): Goggin MJ. Jockes AM: Gas exchange in renal failure I. Dangers of hyperkalemia during anaesthesia. Br Med J 1971; 2: Burger GA. Howard R: Acidosis and K +. Anesth Analg 1993; 76: Udea Issaku. Kamya H. Krishna PR. Acidosis and K +. Anesth Analg 1994; 78: Gronert GA, Theye RA. Effect of on skeletal muscle with immobilization atrophy. Anesthesiology 1974; 40: Horton W.A. Fergusson NV: Hyperkalemia and cardiac arrest after the use of Suxamethonium in intensive care. Anesthesia 1988; 43: Hemming AE, Charlton S, Kelly P. Hyperkalemia, Cardiac arrest. Suxamethonium and intensive care (Correspondence) Anaesthesia. 1990; 45: Hansen D, Suxamethonium induced cardiac arrest and death following 5 days of immobilization. Eur J Anaesthesiology 1998; March, 15: 2: Lee YM; Fountain SW. Suxamethonium and Cardiac arrest. Singapore Med J. 1997; July, 38: 7: Laycock JRD. Laughman E. Suxamethonium induced hyperkalemia following cold injury. Anaesthesia 1986; 41: Dear Members, MEDICO LEGAL QUERY? Of late, cases under CPA, against anaesthesiologists, are increasing throughout the country. Though most of the cases are dismissed, ultimately by the court of law, they are causing lot of tension and worry for the doctors and their families. One of the G.C.Members of ISA, Dr. S. C. Parakh MD (Anaesth), LLM, is well versed in medico- legal aspects from any of the volunteered to answer any of the medico legal queries related to our profession from any of the ISA members. Please contact him at 4-2, Daffodil Apt., DD Colony, Hyderabad shym@hd.vsnl.net.in President, ISA