|Year : 2014 | Volume
| Issue : 4 | Page : 491-496
Neurological outcome of normothermic versus hypothermic cardiopulmonary bypass in simple congenital heart diseases
Amal R Reyad1, Mohamed Adel F Elgamal2
1 Department of Anesthesia and Intensive Care, Mansoura University, Mansoura, Egypt
2 Department of Cardiothorathic Surgery, Mansoura University, Mansoura, Egypt
|Date of Submission||02-Jan-2014|
|Date of Acceptance||10-Feb-2014|
|Date of Web Publication||28-Nov-2014|
Amal R Reyad
Department of Anesthesia and Intensive Care, Mansoura University, Mansoura, 11566
Source of Support: None, Conflict of Interest: None
We hypothesized that normothermic cardiopulmonary bypass (CPB) may provide equivalent results to hypothermic CPB on neurological outcome.
Patients and methods
Forty patients were randomized to one of two groups: group 1 that underwent normothermic CPB (>35°C) and group 2 that underwent mild hypothermic CPB (32°C). Perfusion on bypass was performed by a nonpulsatile pump flow with an average flow rate around 2.4 l/m 2 /min. A pH-stat carbon dioxide management strategy was used. The arterial and jugular venous blood gases, mean cerebral blood flow velocity (CBFV), and pulsatile index were measured as basal, after induction of anesthesia, at the onset of CPB, 20-30-40 min after the CPB, at the cessation of CPB, and at the end of the operation. Neurological outcomes were assessed by computed tomography scanning and Wechsler Preschool and Primary Scale of Intelligence preoperatively, at the third postoperative day and 1 month after surgery. Postoperative ICU variables such as duration of mechanical ventilation, time to extubation, and ICU length of stay were recorded.
There was a significant increase in SjvO 2 and decrease in CeO 2 in the hypothermia group of patients after establishment of hypothermia by 10 and 20 min when compared with the normothermic group (P < 0.05 and <0.01, respectively). The CeO 2 was maximal during normothermic CPB and after rewarming phase of hypothermic CPB. There were no significant changes in computed tomography scanning and Wechsler Preschool and Primary Scale of Intelligence between the studied groups at any time period. There was significant prolongation in duration of postoperative mechanical ventilation, extubation time, and duration of ICU stay in the hypothermic group of patients compared with the normothermic group (P < 0.05).
During CPB for correction of congenital heart defects, the normothermic and hypothermic CPB were comparable with respect to the neurological outcome. However, normothermia permits shorter time on mechanical ventilation, more rapid extubation, and shorter ICU stay time compared with hypothermia.
Keywords: cardiopulmonary bypass, hypothermia, infants, normothermia
|How to cite this article:|
Reyad AR, Elgamal MF. Neurological outcome of normothermic versus hypothermic cardiopulmonary bypass in simple congenital heart diseases. Ain-Shams J Anaesthesiol 2014;7:491-6
|How to cite this URL:|
Reyad AR, Elgamal MF. Neurological outcome of normothermic versus hypothermic cardiopulmonary bypass in simple congenital heart diseases. Ain-Shams J Anaesthesiol [serial online] 2014 [cited 2021 Apr 19];7:491-6. Available from: http://www.asja.eg.net/text.asp?2014/7/4/491/145675
| Introduction|| |
The innovation in surgical techniques and postoperative intensive care could improve outcomes and decreased mortality rates in pediatric cardiac surgery after repair of congenital heart diseases. The use of hypothermic cardiopulmonary bypass (CPB) for pediatric cardiac surgery provides brain protection and reduces the cellular metabolic rate [1,2]. However, the hypothermic CPB induces deleterious effects and may contribute to organ dysfunction [3,4]. Furthermore, the long-term follow-up after hypothermic CPB for neonatal arterial switch operation showed impaired neurodevelopmental outcome .
The normothermic CPB has several potential advantages such as shortening of the duration of CPB, less need for hemodilution, and maintaining the hemoglobin dissociation curve within the normal range allowing better tissue oxygen delivery [6-8]. Many centers are increasingly using the normothermic CPB for pediatric cardiac surgery [6-8].
We hypothesized that the use of normothermic CPB might have comparable neurological outcome on the hypothermic CPB.
The present study aimed to compare jugular venous oxygen saturation (SjvO 2 ), cerebral extraction of oxygen (CeO 2 ), cerebral blood flow velocity, and neurological outcome after the use of normothermic and mild hypothermic (32°C) CPB for correction of congenital heart defects. The primary outcome measure was the SjvO 2 , whereas the secondary outcome measures were CeO 2 , mean cerebral blood flow velocity, pulsatile index (PI), computed tomography (CT), and Wechsler Preschool and Primary Scale of Intelligence at each individual time point.
| Patients and methods|| |
Following ethical approval and obtaining of informed written consent from all patient guardians, 40 children who underwent elective repair of ventricular and atrial septal defects using CPB were included in this prospective randomized blinded comparative study, which was performed at Mansoura University Children Hospital from March 2010 to May 2013.
Patients with pulmonary or renal disease, juvenile diabetes mellitus, clinical or radiological evidence of cerebral or neurological disease, or redo or emergency procedures were excluded from the study.
All surgical procedures were performed by the same surgeons.
All patients were subjected to preoperative clinical, laboratory, and radiological investigations, including total blood count, liver function test, serum creatinine, prothrombin time, activated prothrombin time, chest radiography, and echocardiography. Preoperative neurological examination was performed by an independent pediatric neurologist who was unaware of the randomization code. Baseline brain CT scanning was performed for all studied patients.
On arrival to the holding area, all patients were premedicated with an intramuscular injection of midazolam 0.07 mg/kg and atropine sulfates 0.02 mg/kg, 15 min before induction of anesthesia.
Patients were randomly assigned into two equal groups using computer randomization software-generated codes included in sealed opaque envelopes. In group 1 (n = 20) patients normothermic CPB (>35°C) was used during surgery, whereas in group 2 (n = 20) mild hypothermic CPB (32°C) was used.
Patient monitoring included five-lead ECG, noninvasive arterial blood pressure, and peripheral oxygen saturation.
Anesthetic technique was standardized in all patients.
Anesthesia was induced with fentanyl 5 μg/kg, sevoflurane (1-1.5 MAC), and rocuronium 0.5 mg/kg to provide muscle relaxation. After loss of consciousness, patients were mechanically ventilated by positive-pressure ventilation by face mask at a rate of 20-28 breathes/min with 50% O 2 . After achievement of full relaxation and the targeted MAC, the trachea was intubated with endotracheal tube (ETT) inserted. Normocapnia was maintained throughout. Anesthesia was maintained with 0.5-1 MAC and fentanyl 0.05 μg/kg/min, to maintain state entropy values less than 50. Rocuronium 0.3 mg/kg/min infusion was used to maintain surgical relaxation.
A radial artery was catheterized. The right jugular bulb was catheterized using a single lumen 4 Fr catheter through Seldinger technique for measurements of central venous pressure and systemic and cerebral hemodynamic and blood sampling . The catheter was advanced cephalad until the resistance of the roof of jugular bulb was felt, then was withdrawn ~1 cm. The catheter position was then confirmed by fluoroscopy to verify the correct position of the catheter tip at the base of the skull. Both catheters were continuously flushed with heparinized normal saline.
A standard median sternotomy was used for all patients. The ascending aorta, superior vena cava (SVC), and inferior vena cava (IVC) were cannulated for CPB using a membrane oxygenator and a roller pump with a 40 μm arterial line filter after achievement of an activated clotted time above 480 s with the use of heparin (300-400 IU/kg). A nonpulsatile pump flow with an average flow rate of 2.4 l/m 2 /min was used. A pH-stat carbon dioxide management strategy was used. After aortic cross clamping, all patients received cold (5°C) crystalloid cardioplegia. The cardioplegia solution contained 500 ml of Ringer acetate, magnesium sulfate 1 g, 20 mEq of potassium chloride, 100 mg of lidocaine, 10 ml of NaHCO 4 8.4%. Antegrade cardioplegia was delivered as initial 15-20 ml/kg through the aortic root over 4-8 min by a roller pump, and subsequent 7.5-10 ml/kg of the same solution was administered after 20 min. Hematocrit value was maintained between 20 and 25% during CPB, with addition of packed red blood cells as necessary. During CPB, anesthesia was maintained with ketamine 2 mg/kg/h, rocuronium 0.3 mg/kg/h, and fentanyl 0.03 µg/kg/min, and PaCO 2 was adjusted at 35-40 mmHg. The target nasopharyngeal temperatures were 32 and 36°C in the mild hypothermic and normothermic groups, respectively.
After completion of surgical repair, rewarming of the patients to a nasopharyngeal temperature of 36°C was performed, and CPB was gradually discontinued using inotropic support according to the heart rate, rhythm, right atrial filling pressure, after load, and contractility of heart. Phenylephrine infusion was mostly used to maintain mean arterial pressures of 40-45 mmHg. Dobutamine and milrinone were used for neonatal patients.
Arterial and jugular bulb blood samples were withdrawn simultaneously. Venous and arterial samples were analyzed for blood gasometry. The CeO 2 was calculated as the difference between arterial and jugular oxygen saturation . Velocities of cerebral blood flow were monitored by transcranial Doppler through fontanel or transtemporal window . End-diastolic, peak systolic, and mean cerebral blood flow velocities were recorded automatically. The mean cerebral blood flow velocity was defined as: 1/3 (peak systolic flow velocity+2×end-diastolic flow velocity). It was collected with an M-ENTROPYTM module of the S/5TM Anesthesia Monitor (DatexOhmeda, Helsinki, Finland) . The PI (peak systolic−end-diastolic velocities/mean flow velocity) was calculated .
The arterial and jugular venous blood gases, mean CBFV, and PI were measured at the following time intervals:
(2) After induction of anesthesia and before initiation of surgery,
(3) At the onset of CPB,
(4) 20 min after the CPB (after 10 min of cooling to 32°C in the hypothermic group),
(5) 30 min after the CPB (after 20 min of cooling to 32°C in the hypothermic group),
(6) 40 min after the CPB (after rewarming to 36°C in the hypothermic group),
(7) At the cessation of CPB, and
(8) At the end of the operation.
Neurological outcomes were assessed by serial brain CT scanning preoperatively, on the third postoperative day and 1 month after surgery for gross neurological dysfunction. The neurocognitive status was evaluated using the Wechsler Preschool and Primary Scale of Intelligence, 3rd ed., at the same time intervals . Postoperative ICU variables such as duration of mechanical ventilation, time to extubation, and ICU length of stay were recorded.
Sample size was calculated using the one-tail t-test for two independent groups proportions for means analysis of SjvO 2 in G* power 3.1.1 program. According to a pilot study on 10 patients (five patients in each group), we calculated that 18 patients per group were suitable to give significant P-value less than 0.05, with 95% confidence interval with an actual power of 85.5%. We added two patients in each group to avoid patient dropout.
Statistical analysis of data was performed using statistical package for the social sciences (SPSS, version 18; SPSS Inc., Chicago, Illinois, USA) program. The description of the data was given in the form of mean (SD) and numbers (%). Continuous data were compared with the independent t-test and categorical data by the χ2 -test or Fisher's exact test as appropriate. Intragroup differences of repeated measures were analyzed with repeated measurement analysis of variance. When F value was less than 0.05, post-hoc test was performed by the Tukey HSD test. The P-value less than 0.05 was considered statistically significant.
| Results|| |
The demographic data of the studied groups were comparable ([Table 1]).
With respect to the SjvO 2 , there were no changes in the basal SjvO 2 between the studied groups. There was significant increase in SjvO 2 in the hypothermia group of patients after establishment of hypothermia by 10 and 20 min when compared with the normothermic group (P < 0.05 and <0.01, respectively) ([Table 2]).
|Table 2 Jugular bulb venous oxygen saturation and cerebral extraction of oxygen in the studied groups|
Click here to view
The results of this study demonstrated no significant changes in the basal values of CeO 2 between the studied groups. There was significant decrease in CeO 2 in the hypothermic group after 20 and 30 min of CPB compared with the normothermic group during the same study periods (P < 0.05 and <0.01, respectively) ([Table 2]). The CeO 2 was maximal during normothermic CPB and after rewarming phase of hypothermic CPB. After weaning from CPB, the CeO 2 was significantly greater than the preoperative values in both groups (P < 0.05). The finding of this study showed no significant changes in the basal values of mean cerebral blood flow velocity between the studied groups. There was significant decrease in the mean cerebral blood flow velocity after 20 and 30 min of CPB in the hypothermic group of patients compared with the normothermic group at the same time intervals (P < 0.05 and <0.01, respectively) ([Table 3]). There was significant decrease in the values of mean cerebral blood flow velocity in both groups after initiation of CPB until cessation of CPB compared with the basal values of the same group.
With respect to the basal values of PI of cerebral blood flow, there were no significant changes between the two groups. There was significant decrease in PI in the hypothermic group after 20 and 30 min of CPB compared with the normothermic group during the same time period (P < 0.05 and <0.01, respectively) ([Table 3]).
|Table 3: Mean cerebral blood fl ow velocity (mmHg) and pulsatile index (mmHg) in the studied groups|
Click here to view
There were no significant changes in the basal values of CT scanning and the Wechsler Preschool and Primary Scale of Intelligence between the studied groups. In addition, there were no significant changes between the studied groups with respect to the CT scan and Wechsler preschool scale on the third day and after 1 month ([Table 4]).
|Table 4 Neurological examination and computed tomography study preoperatively, on the third day postoperatively, and after 1 month of the studied groups|
Click here to view
There was significant prolongation in duration of postoperative mechanical ventilation, extubation time, and duration of ICU stay in the hypothermic group of patients compared with the normothermic group (P < 0.05) ([Table 5]).
| Discussion|| |
Good cerebral protection remains a challenge for cardiac surgeons and anesthesiologists. Hypothermia during CPB no doubt decreases tissue metabolism, but considering its adverse effects the net benefits in comparison with normothermia is questionable. The present study demonstrated that cerebral oxygenation, estimated by SjvO 2 , was well maintained throughout mild hypothermic CPB but was decreased during normothermic CPB, whereas cerebral demand of oxygen, estimated by CeO 2 , was decreased during hypothermic CPB and increased during normothermic CPB. In addition, there were decreased mean cerebral blood flow velocity and PI in the hypothermic group of patients compared with the normothermic group. In accordance with our finding, Chowdhury et al. found increased SjvO 2 and decreased CeO 2 during hypothermic CPB and decreased SjvO 2 and increased CeO 2 during normothermic CPB. They reported that hypothermia reduced cerebral metabolic oxygen consumption to a proportionately greater extent than cerebral blood flow, resulting in 'luxuriant perfusion', which means uncoupling of CBF and CMRO 2 during hypothermia . Coupling of cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO 2 ) is thought to be important to match regional blood flow to metabolic demand. In this study, the increased SjvO 2 and decreased CeO 2 during hypothermia provides physiological evidence for the 'luxuriant perfusion' phenomenon. Other authors reported that hypothermia reduced oxygen demand; hence, it was effective in brain protection but it impaired vasomotoricity and cerebral oxygen regulation. It also alters energetic metabolism and increases intracranial pressure and rewarming-induced neurological injury . In the present study, jugular venous desaturation and increased cerebral oxygen extraction during the rewarming phase of CPB indicate inadequate CBF in proportion to oxygen consumption and greater oxygen extraction during hypothermia compared with normothermic CPB. In agreement with our results, the findings of other investigators demonstrated similar changes in near infrared spectroscopy, SjvO 2 , or CBF/CMRO 2 during cooling [15-17]. Our study demonstrated that there were no significant changes between normothermic CPB and hypothermic CPB with respect to gross neurological dysfunction and neurocognitive status detected by CT and the Wechsler Preschool and Primary Scale of Intelligence, respectively, during any time period up to 1 month postoperatively. In accordance with our results, Plourde et al. (18) found no difference in postoperative CT or cognitive function between the normothermic and hypothermic groups. In contrast to our results, some investigators found more observed postoperative neurophysiological dysfunction in normothermia than hypothermia [19,20]. They examined postoperative neurophysiological dysfunction after CPB at 28, 32, and 37°C and found that there was a difference in postoperative cognitive function between the normothermic (37°C) and hypothermic (28°C) groups but not between the mild hypothermic (32°C) and hypothermic (28°C) groups. Previously, others examined the effects of normothermia (37°C) and hypothermia (30°C) on SjvO 2 during CPB, which indicates the global balance of cerebral blood flow and the cerebral metabolic rate and is used to estimate the adequacy of flow/metabolism coupling in the brain and the associated postoperative cognitive function .
In the current study, the normothermic group showed more rapid recovery as shown by shorter time of mechanical ventilation, shorter time to extubation, and shorter length of ICU stay compared with the hypothermic group. In accordance with our results, some investigators reported that lungs are very sensitive to CPB, and hypothermia could increase the capillary leakage more than normothermia by inducing microcirculatory dysfunction and impairing endothelial responses [8,22]; this explains the prolonged time of mechanical ventilation, time to extubation, and ICU stay after hypothermic CPB.
| Conclusion|| |
During CPB for correction of congenital heart defects, the normothermic and hypothermic CPB were comparable with respect to the neurological outcome, despite better cerebral oxygenation and lesser CBF during hypothermia compared with normothermia. However, normothermia permits shorter time on mechanical ventilation, more rapid extubation, and shorter ICU stay time compared with hypothermia.
| Acknowledgements|| |
| References|| |
Hanley FL. Religion, politics...deep hypothermic circulatory arrest. J Thorac Cardiovasc Surg 2005; 130:1236.
Jonas RA. Normothermic cardiopulmonary bypass in pediatric surgery reply. J Thorac Cardiovasc Surg 2002; 123:194.
Pigula FA, Siewers RD, Nemoto EM. Hypothermic cardiopulmonary bypass alters oxygen/glucose uptake in the pediatric brain. J Thorac Cardiovasc Surg 2001; 121:366-373.
Lewis ME, Al-Khalidi AH, Townend JN, Coote J, Bonser RS. The effects of hypothermia on human left ventricular contractile function during cardiac function. J Am Coll Cardiol 2002; 39:102-108.
Hovels-Gurich HH, Seghaye MC, Sigler M, Kotlarek F, Bartl A, Neuser J, et al.
Neurodevelopmental outcome related to cerebral risk factors in children after neonatal arterial switch operation. Ann Thorac Surg 2001; 71:881-888.
Durandy YD, Younes M, Mahut B. Pediatric warm open heart surgery and prolonged cross-clamp time. Ann Thorac Surg 2008; 86:1941-1947.
Caputo M, Bays S, Rogers CA, Pawade A, Parry AJ, Suleiman S, Angelini GD. Randomized comparison between normothermic and hypothermic cardiopulmonary bypass in pediatric open-heart surgery. Ann Thorac Surg 2005; 80:982-988.
Pouard P, Mauriat P, Ek F, Haydar A, Gioanni S, Laquay N, et al.
Normothermic cardiopulmonary bypass and myocardial cardioplegic protection for neonatal arterial switch operation. Eur J Cardiothorac Surg 2006; 30:695-699.
Feldman Z, Robertson C. Monitoring of cerebral hemodynamics with jugular bulb catheters. Crit Care Clin 1997; 13:51-77.
Aaslid R, Markwalder T, Nornes H. Noninvasive transcranial doppler ultrasound recording of flow velocity in basal cerebral arteries. J Neurosurg 2010; 112:769-774.
Ainslie PN, Cotter JD, George KP, Lucas S, Murrell C, Shave R, et al.
Elevation in cerebral blood flow velocity with aerobic fitness throughout healthy human ageing. J Physiol 2008; 586:4005-4010.
Zweifel C, Czosnyka M, Carrera E, de Riva N, Pickard JD, Smielewski P. Reliability of the blood flow velocity pulsatility index for assessment of intracranial and cerebral perfusion pressures in head-injured patients. Neurosurgery 2012; 71:853-861.
Snookes SH, Gunn JK, Eldridge BJ, Donath SM, Hunt RW, Galea MP, Shekerdemian L. A systematic review of motor and cognitive outcomes after early surgery for congenital heart disease. Pediatrics 2010; 125:e818-e827.
Chowdhury UK, Airan R, Malhotra P, Reddy SM, Singh R, Rizvi A, et al.
Relationship of internal jugular venous oxygen saturation and perfusion flow rate in children and adults during normothermic and hypothermic cardiopulmonary bypass. Hellenic J Cardiol 2010; 51:310-322.
Kurth CD, Steven JM, Nicolson SC, Jacobs ML. Cerebral oxygenation during cardiopulmonary bypass in children. J Thorac Cardiovasc Surg 1997; 113:71-78.
Mezrow CK, Gandsas A, Sadeghi AM, Midulla PS, Shiang HH, Green R, et al.
Metabolic correlates of neurologic and behavioral injury after prolonged hypothermic circulatory arrest. J Thorac Cardiovasc Surg 1995; 109:959-975.
Greeley WJ, Kern FH, Ungerleider RM, Boyd JLIII, Quill T, Smith LR, et al.
The effect of hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral metabolism in neonates, infants, and children. J Thorac Cardiovasc Surg 1991; 101:783-794.
Plourde G, Leduc AS, Morin JE, DeVarennes B, Latter D, Symes J, et al.
Temperature during cardiopulmonary bypass for coronary artery operations does not influence postoperative cognitive function: a prospective, randomized trial. J Thorac Cardiovasc Surg 1997; 114:123-128.
Mora CT, Henson MB, Weintraub WS, Black AM, Lopatatzidis A, Day CJ, et al.
The effect of temperature management during cardiopulmoary bypass on neurologic and neuropsychologic outcomes in patients undergoing coronary revascularization. J Thorac Cardiovasc Surg 1996; 112:514-522.
Regragui I, Birdi I, Izzat MB, Black AM, Lopatatzidis A, Day CJ, et al.
The effects of cardiopulmonary bypass temperature on neuropsychologic outcome after coronary artery operations: a prospective randomized trial. J Thorac Cardiovasc Surg 1996; 112:1036-1045.
Kadoi Y, Kawahara F, Saito S, Morita T, Kunimoto F, Goto F, Fujita N. Effects of hypothermic and normothermic cardiopulmonary bypass on brain oxygenation. Ann Thorac Surg 1999; 68:34-39.
Yamada S. Impaired endothelial responses in patients with deep hypothermic cardiopulmonary bypass. Kurume Med J 2004; 51:1-7.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]