Comparison of isothermic and cold cardioplegia in paediatric cardiac surgery

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Background Use of isothermic blood cardioplegia is not widely reported in paediatric cardiac surgical practice. It is a prospective comparative study of isothermic versus cold cardioplegia done from July 2005 to October 2005. Methods Fifty patients
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  IJTCVSReddy et al 12007; 23: 1-4Cardioplegia Comparison of isothermic and cold cardioplegia in paediatriccardiac surgery Pramod Reddy Kandakure, M.Ch., Nagarajan Ramdoss, MD, Veluthedath Achuthan Akhilesh, DPT,Anil Kumar Dharmapuram, M.Ch., Rohit Agarwal, MD, Kona Samba Murthy, M.Ch Department of Pediatric Cardiac Surgery, Apollo Children’s Heart Hospital, Jubilee Hills, Hyderabad, India Address for correspondence: Dr. K.S. Murthy, Chief Pediatric Cardiac SurgeonApollo Children’s Heart Hospital, Jubilee Hills,Hyderabad – 500033Ph# 91 40 23600852, 23607777 - Ext: 3048. Cell: 91 9849298001Fax: 91 40 23608050E-mail: konasmurthy@gmail.com© IJTCVS 097091342310307/59 Received-31/07/06; Review Completed-07/09/06; Accepted-14/12/06. Introduction Outcome depends not only on good surgicalcorrection but also on good myocardial protection, toreduce postoperative morbidity and mortality.Hypothermia has remained as an integral part of myocardial protection during cardiopulmonary bypass.Bigelow et al, described, hypothermia as the single mostimportant component of myocardial protection 1 . Thereason behind this is based on evidence indicating thatmyocardial hypothermia significantly diminishescardiac metabolism 2 . Despite the benefits of hypothermia there are major disadvantages to thismodality of myocardial protection. Liechtenstein firstintroduced the concept of normothermic perfusion andnormothermic cardioplegia for myocardial protection 4 .Isothermic blood cardioplegia was introduced formyocardial protection, for providing more physiologicalmyocardial metabolic activity 17 . Isothermic bloodcardioplegia is not widely used in paediatric cardiacsurgical practice. In this prospective study we compareisothermic blood cardioplegia with conventional cold blood cardioplegia for myocardial metabolic activity,myocardial protection and contractile function. Material and Methods From July 2005 to October 2005 fifty pediatric patientsundergoing open-heart surgery were taken up for study.They were divided into two equal groups. In group I, Abstract Background: Use of isothermic blood cardioplegia is not widely reported in paediatric cardiac surgicalpractice .It is a prospective comparative study of isothermic versus cold cardioplegia done from July 2005 toOctober 2005.  Methods: Fifty patients were selected and divided into two equal groups. Group I, Isothermic bloodcardioplegia, patients were cooled to 30 0  C, and cardioplegia given at the same temperature as circulatingblood in cardiopulmonary bypass and repeated at 20 minutes. Cardioplegic heat exchanger was not utilized incardiopulmonary bypass circuit. In group II, conventional cold cardioplegia, patients were cooled to 28-30 0  C.Cardioplegia was given at 7-10 0  C and was repeated every 30 minutes. To assess myocardial metabolic activity,myocardial oxygen consumption (MVO 2 ), myocardial glucose uptake, myocardial lactate and acidosis weremeasured, using arterial and coronary venous blood samples. Results: Mean cardiopulmonary bypass time was significantly shorter in children receiving isothermicblood cardioplegia(69 v/s 96 minutes).Serum lactate after cardiopulmonary bypass in isothermic bloodcardioplegia were lower (1.9 v/s2.9).There was less metabolic acidosis in isothermic group (pH 7.37 v/s 7.34).Glucose uptake was higher in isothermic group. Myocardial contractile function was slightly better in theisothermic group (Ejection Fraction -62 v/s 60 %). Conclusion: Myocardium utilizes more oxygen and glucose after isothermic cardioplegia, but lactate andacid production were less. However they are not statistically significant and operative outcome was notdifferent. Isothermic blood cardioplegia is a safe and cost effective alternative to conventional coldcardioplegia for children undergoing open heart surgery. (Ind J Thorac Cardiovasc Surg, 2007; 23: 1–4) Key words: Cardiopulmonary bypass, Surgery, Open heart surgery   Original articles 59-06(OA).P652/27/2007, 4:17 PM1  2 Reddy et alIJTCVS Cardioplegia2007; 23: 1-4 Isothermic blood cardioplegia, patients were cooled to30°C and cardioplegia was given at the sametemperature as perfusate in cardiopulmonary bypassand repeated at 20 minutes interval if required. Sincethe maximum oxygen consumption is during theterminal phase of cardioplegic arrest two different timeintervals were selected for warm and cold bloodcardioplegia. Cardioplegic heat exchanger was notutilized in cardiopulmonary bypass circuit.In group II, the conventional cold cardioplegia,patients were cooled to 28-30°C. Cardioplegia was givenat 7-10°C and was repeated every 30 minutes if required.Cases which were included in this study are AtrialSeptal Defect, Ventricular Septal Defect, and Tetrologyof Fallot.To assess myocardial metabolic activity, myocardialoxygen consumption (mvO 2 ), myocardial glucoseuptake, myocardial lactate and acidosis were measuredusing arterial and coronary venous blood samples.Arterial samples were obtained from cardioplegia line.Coronary venous blood samples were obtained directlyfrom coronary sinus just before beginning and just before the end of first cardioplegia. Subsequent samplesare taken just before giving next cardioplegia & just before releasing cross clamp.Each blood sample was assayed for hemoglobin (Hb),partial pressure of oxygen (pO 2 ), carbon dioxide (pCO 2 ),pH, oxygen saturation(O 2  sat), lactate and glucose levels.Oxygen content was calculated as follows: oxygencontent =1.39 hemoglobin x oxygen saturation + 0.0031oxygen tension. Myocardial oxygen extraction (O 2  Ext)was calculated as oxygen content of the cardioplegic blood minus the oxygen content of coronary venouseffluent. Myocardial oxygen consumption was thencalculated by simply multiplying the oxygen extractionvalue by the flow rate of blood cardioplegia (mvO 2  =O 2 Ext x flow). The change of temperature is a continuousdynamic process during cardioplegic arrest, hence wecalculated the oxygen content and variables at astandardized 37°c.Myocardial lactate levels were calculated as lactatevalue of coronary venous effluent minus the lactatevalue of cardioplegic solution.In the postoperative period, all patients weremonitored for arrhythmia, need for inotropic supportand Ejection Fraction for myocardial function.Postoperative haemodynamic stability, the need forinotropic support, postoperative ejection fraction andclinical outcome are considered as the indicators forassessing how well myocardium is protected. However,myocardial metabolic measurements have beenreported to be better indicators. The present study hasshown how cardioplegic temperature can affect cardiacmetabolism. Statistical Analysis:  All data were entered in SPSS(Statistical Package for the Social Sciences) statisticalanalysis program for windows. The unpaired student’st-test was used to compare continuous variables.Comparisons of clinical parameters were evaluated bythe Chi-square analysis. Data are expressed as themean± standard deviation of the mean. Statisticalsignificance was assumed at a probability level of lessthan 0.05. Results Patient characteristics and intraoperative data weresimilar in the two groups, Cardioplegic infusion rates;aortic root pressures were similar in both groups.Both groups were compared in various aspects.Median age is 38±12.5 months in cold cardioplegiagroup whereas it was 50±10.7 months in isothermicgroup. M:F ratio was 15:10 in group I and 13:12 in groupII. Median Weight was 10.25±7.2 Kgs in group Icompared to 13 ± 6.8 in group II.As shown in Table I, Mean cardiopulmonary bypasstime is less in isothermic cardioplegia group.Comparison of pH values (Table II) shows more acidosisin cold cardioplegia group. Table 1. Comparison of mean aortic Xclamp time and meancardiopulmonary bypass time in two groups.Cold cardioplegiaIsothermic(Group I)Cardioplegia(Group II) Mean CPB time96.27 ±49.4769.81 ±19.02(minutes)Mean Aortic cross34.63 ±21.4829.45 ±12.2clamp time(minutes) P value – not significant Table 2.   Comparison of pH values in two groups. PH0PH1PH2 Cold cardioplegia (Group I)7.45±0.087.47±0.077.34±0.14Isothermic cardioplegia7.46±0.087.54±0.087.37±0.07 (Group II) P value – not significant The calculated values for myocardial O 2 Consumption and glucose uptake were higher inisothermic group compared to cold cardioplegia group 59-06(OA).P652/27/2007, 4:17 PM2  IJTCVSReddy et al 32007; 23: 1-4Cardioplegia (Table III).Myocardial lactate production was greater incold cardioplegia group .Ejection fraction was slightly better in isothermic cardioplegia group. Even thoughthe values are different in two groups, they are notstatistically significant.effects like ventricular fibrillation, arrhythmias,promotion of rouleau formation, and potential forphrenic nerve damage, It has been shown that utilizationof glucose and ATP generation are decreased to a greaterdegree 3 . Several studies suggested that hypothermiccardioplegia may damage the myocardium and vascularendothelium. 16 In our experience average time of cardiopulmonary bypass in cold cardioplegia is 96 minutes and that inisothermic cardioplegia 69 minutes. Time interval oncardiopulmonary bypass before applying cross clampand after releasing of cross clamp is very less as the timespent in cooling and rewarming of the patient wasminimalPostoperative hemodynamic stability, the need forinotropic support and postoperative ejection fractionand clinical outcome are considered as the indicatorsused in assessing how well myocardium is protected.However, myocardial metabolic measurements have been reported to be better indicators 19 . The present studyhas shown how cardioplegic temperature can affectcardiac metabolism. Myocardium utilizes more oxygenand more glucose while producing less lactate whencardioplegia temperature is increased to circulating blood temperature. This aerobic state of myocardialmetabolism during isothermic cardioplegia might be thereason for early recovery observed in the hearts.The results of our study have demonstrated that acardioplegic heart consumes more glucose and oxygenwhile producing less lactate during isothermiccardioplegia infusions in comparison to coldcardioplegic solution. This more aerobic status of myocardial metabolism during cardioplegic reinfusionsin the arrested heart might be the reason for the earlyrecovery observed in the hearts protected by isothermic blood cardioplegia. It has been postulated that lactateproduction is a reflection of anaerobic metabolism, whileglucose uptake and oxygen extraction reflect the aerobicmetabolic state of myocardium 18 .Isothermic blood cardioplegia is cost effectivealternative as heat exchanger is not utilized. Conclusion Myocardium utilizes more oxygen and glucose afterisothermic cardioplegia, but lactate and acid productionwere less, however operative outcome was not different.Time spent in cooling and rewarming of the patient wasless in isothermic group. Isothermic blood cardioplegiais a safe and cost effective alternative to conventionalcold cardioplegia for children undergoing open-heartsurgery. Table 3.   Comparison of O 2  extraction, myocardial lactate,glucose extraction and EF in two groups.ColdIsothermicCardioplegiaCardioplegia Oxygen Consumption4.01 ± 4.35.79 ± 4.6(mL /dL)Lactate Levels (mmols/L)2.9 ±1.31.9 ± 0.85Glucose Extraction (mg/dL)8.4±5.69.2±4.2Ejection Fraction(%)60.7±2.362 ±3.2 P value – not significant In all patients, cardiopulmonary bypass wasterminated in the first attempt. There were no hospitaldeaths, no neurological deficit. Discussion Good myocardial protection has remained achallenge for cardiac surgeons. In general, most changesin paediatric myocardial protection have been derivedfrom the adult cardiac experience. However in view of the structural, functional and metabolic differences,extrapolation of adult cardio protective strategies to thepediatric patients is fundamentally imprudent andpotentially harmful 5-8 .Buckberg and colleagues introduced warm bloodcardioplegia in1977 9 . It was used as a method to decreasethe reperfusion injury that occurred after cross clampremoval and was delivered as a terminal hot shot 10. Concept of warm blood cardioplegia induction wasintroduced in 1983.It was shown that warm bloodinduction resulted in active resuscitation and improvedtolerance of the myocardium to the subsequent ischemicperiod 11 . Warm blood cardioplegia has been shown toresult in improved metabolic and functional recoveryof myocardium in many experimental models 12,13 .Decreasing temperatures during cardiopulmonary bypass no doubt decreases tissue metabolism but causesintracellular swelling, sodium accumulation,impairment of oxygen dissociation, decrease inmembrane fluidity, inhibition of calcium uptake insarcoplasmic reticulum 3 . The net benefits of coldcardioplegia in comparison to tepid cardioplegia isquestionable because hypothermia has some adverse 59-06(OA).P652/27/2007, 4:17 PM3  4 Reddy et alIJTCVS Cardioplegia2007; 23: 1-4 Acknowledgement We thank Dr. Sunil Kumar Swain (Pediatric CardiacSurgeon), Dr. Vincent O. (Cardiac Surgeon); Mr. AmarMane (Perfusionist), and Mr. Ravi, the secretary, for theirhelp to prepare the manuscript. References 1.Bigelow WG, Lindsay WK, Greenwod WF. Hypothermia: itspossible role in cardiac surgery an investigation of factorsgoverning survival in dogs at low body temperatures.  Ann Surg. 1950; 132: 849–66.2.Russ C, Lee JC. Effect of hypothermia on myocardial metabolism.  Am J Physiol.  1965; 208: 1253–58.3.Lyons JM; Raison JK.A temperature induced transition inmitochondrial oxidation: contrast between cold and warm blooded animals. Comp Biochem Physiol.  1970; 37: 405–11.4.Lichtenstein Sv, Ashe KA, el Dalati H, Cusimano RJ, Panos A ,Slutsky AS. Warm heart surgery.  J thorac cardiovasc Surg  1991;101: 269–74.5.Casteneda AR, Jonas RA, Mayer JE, Hanley FL. Myocardialpreservation in immature heart. In: Castaneda AR, Jonas RA,Mayer JE, Hanley FL,editors. Cardiac surgery of neonate andinfant. Philadelphia: WB Saunders. 1994.p-41–54.6.Hamman JW Jr. Myocardial protection in the immature heart.  Ann Thorac surgery  1995; 60: 839–42.7.Romero TE, Friedman WF. Limited left ventricular response tovolume overload in neonatal period. Pediatri Res.  1979; 13: 910–15.8.Allen BS, Barth MJ, Ilbani MN, Paediatric myocardial protection:an overview. Semin thorac Cardiovas Surg.  2001; 13: 56–72.9.Cooper N, Brazier JR, Mcconnell DN, Buckberg GD. Studies of effects of hypothermia on regional myocardial blood flow andmetabolism during cardiopulmonary bypass. IV. Topical atrialhypothermia in normothermic beating hearts.  J Thorac CardiovascSurg.  1977; 731: 195–200.10.Lazar HL, Buckberg GD, Manganaro AJ, Foglia RP, Becker H,Mulder DG, et al. Reversal of ischemic damage with secondary blood cardioplegia.  J Thorac Cardiovasc Surg.  1979; 78: 685–97.11.Rosenkranz ER, Buckberg GD, Laks H, Mulder DG. Warminduction of cardioplegia with glutamate enriched blood incoronary patients with cardiogenic shock who are dependenton ionotropic drugs and intraaortic ballon support.  J ThoracCardiovasc Surg. 1983; 86: 507–18.12.Christakis GT, Koch JP, Deemer KA, frames SE, Sinclair L, ChenE,et al. A randomized study of systemic effects of warm heartsurgery.  Ann Thorac Surg.  1992; 54: 449–57.13. Jacquet LM, Noirhamme PH, Van Dyck MJ, El Khoury GA, MattaAJ, Goenen MJ, et al. Randomised trial of intermittent antegradewarm blood versus cold crystalloid cardioplegia.  Ann thorac Surg. 1999; 67: 471–77.14.Guyton RA, Mellitt RJ, Weintraub WS.A critical assessment of neurological risk during warm heart surgery.  J Card Surg.  1995;10: 488–92.15.Badak MI, Gurcun U ,Discigil B, Boga M, Ozkisacik EA, AlayuntEA. Myocardium utilizes more oxygen and glucose during tepid blood Cardioplegic infusion in arrested heart. Int Heart J.  2005;46: 219–29.16.Allen BS, Buckberg GD, Rosenkranz ER, Plested W, Skow J,Mazzei E, et al. Topical cardiac hypothermia in patients withcoronary disease. An unnecessary adjunct to cardioplegicprotection and cause of pulmonary morbitity.  J Thorac CardiovascSurg.  1992; 104: 626–3117.Hayashida N, Weisel RD, Shirai T, Thonomidis JS, Ivanov J,Carson SM, et al. Tepid antegrade retrograde cardioplegia.  AnnThorac Surg.  1995; 59: 723–29.18.Hayashida N, Isomura T, Sato T, Maruyama H, Higashi T,Arinaga K, et al. Minimally diluted tepid blood cardioplegia.  Ann thorac Surg. 1998; 65: 615–21.19.Engelman RM, Plcet AB, Rousou JA, Flack JE 3rd, Deaton DW,Gregory CA, et al .What is the best perfusion temperature forcoronary revascularization?  J Thorac Cardiovasc Surg.  1996; 112:1622–32. 59-06(OA).P652/27/2007, 4:17 PM4
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