Cerebral Oxygen Monitoring during Neonatal Cardiopulmonary Bypass and Deep Hypothermic Circulatory Arrest

We would like to comment on the letter to the editor from Dr. Nollert et al. concerning our paper, Cerebral Oxygen Monitoring during Neonatal Cardiopulmonary Bypass and Deep Hypothermic Circulatory Arrest, which was published in Thorac Cardiovasc Surg [1] [2].

First of all, we agree with Dr. Nollert et al. that the results of our experimental study using the Criticon cerebral oxymeter are similar to their results using other devices. Indeed, according to our experience, similar patterns of changes in intracellular and intravascular parameters before and after deep hypothermic circulatory arrest were found in different experimental settings using different small-animal rabbit and neonatal piglet models with extremely low bodyweight (2 kg). This underlines the validity and accuracy of the Criticon device. Our extensive experiments also used different cerebral oxymeters, including the Hamamatsu and INVOS devices by Somanetics 3. All of them showed similar changes with respect to extreme changes in physiological parameters such as temperature, hematocrit and deep hypothermic circulatory arrest 1 4. Different changes were found in the initial base line values, but no significant differences were found in the trend of changes. We appreciate the published papers of Nollert et al. and the Group of Dr. Jonas in this field 5 6 7 8. However, the aim of our paper was to show our experience and our results in a neonatal animal model using mini-piglets. Citation of a large number of relevant studies was not possible, and was not the aim of the article. The claim that the device has been withdrawn from the market is not correct 2. The device is no longer on the product list of the new owner of Criticon, Johnson and Johnson, for marketing reasons. The devices are still in use in our laboratory and by others since we have not had any impression of incorrect or non-relevant measurements of cerebral oxygenation in clinical practice or in animals. We agree with Dr. Nollert that measurements of intracellular oxygenation according to the cytochrome signal are difficult. However, excellent experimental studies conducted in the laboratories of Dr. D. Delpy in London, which have been published in several papers by Cooper et al., have confirmed that changes in the cytochrome oxydase measured by NIRS are very much related to changes in cellular mitochondrial oxygenation and histopathological changes in the brain 5 9 10 11 12.

As we reported in our papers, changes in intracellular oxygenation are not anticipated when cerebral perfusion and cardiac output are adequate as is the case when full-flow CPB is used. Thus, in these hemodynamic settings without significant alteration in cerebral perfusion, changes in intravascular oxygenation such as the oxygenated haemoglobin signal are more related to physiological parameters such as perfusion pressure, flow rate, haemoglobin and temperature.

The aim of our experimental studies was to evaluate neuroprotective strategies in neonatal cardiac surgery. In addition to the evaluation of changes in cerebral oxygenation according to CPB and DHCA as presented in this paper, preliminary new results show that the measurement of cerebral oxygenation using the Criticon device shows differences in protective action after hemodynamic and pharmacological neuroprotective interventions. The changes correlated to quantitative histological evaluation and molecular assessment in the brain cortex. These results will be published soon.

We recommend the use of cerebral monitoring by NIRS, independently of the device used, particularly in conditions with altered cerebral perfusion and systemic hemodynamics. Alternative accurate non-invasive methods for the evaluation of brain oxygenation are not available as yet, and need to be developed in the future.

References

• 1 Abdul-Khaliq H, Troitzsch D, Schubert S, Wehsack A, Bottcher W, Gutsch E, Hubler M, Hetzer R, Lange P E. Cerebral oxygen monitoring during neonatal cardiopulmonary bypass and deep hypothermic circulatory arrest.  Thorac Cardiovasc Surg. 2002;  50 77-81
• 2 Nollert G, Reichart B. Cerebral oxygen monitoring during cardiopulmonary bypass and deep hypothermia circulatory arrest by H. Abdul-Khalig et al.  Thoracic Cardiovascular Surg. 2002;  50 77, 254
• 3 Abdul-Khaliq H, Weipert T h, Uhlig R, Peeters B, Alexi-Meskishvili V, Felix R, Kuppe H, Hetzer R, Lange P E. Das Serum S-100 Protein nach Korrekturoperationen angeborener Herzfehler im Kleinkindesalter: Beziehung zur Veränderungen der intraoperativen zerebralen Oxygenierung.  Intensivmed. 2000;  37 1-8
• 4 Abdul-Khaliq H, Schubert S, Troitzsch D, Huebler M, Boettcher W, Baur M O, Lange P E. Dynamic changes in cerebral oxygenation related to deep hypothermia and circulatory arrest evaluated by near-infrared spectroscopy.  Acta Anaesthesiol Scand. 2001;  45 696-701
• 5 Shin'oka T, Nollert G, Shum-Tim D, du P lessis, Jonas R A. Utility of near-infrared spectroscopic measurements during deep hypothermic circulatory arrest.  Ann Thorac Surg. 2000;  69 578-583
• 6 Nollert G, Nagashima M, Bucerius J, Shin'oka T, Lidov H G, du Plessis A, Jonas R A. Oxygenation strategy and neurologic damage after deep hypothermic circulatory arrest. II. hypoxic versus free radical injury.  J Thorac Cardiovasc Surg. 1999;  117 1172-1179
• 7 Nollert G, Nagashima M, Bucerius J, Shin'oka T, Jonas R A. Oxygenation strategy and neurologic damage after deep hypothermic circulatory arrest. I. Gaseous microemboli.  J Thorac Cardiovasc Surg. 1999;  117 1166-1171
• 8 Nollert G, Mohnle P, Tassani-Prell P, Uttner I, Borasio G D, Schmoeckel M, Reichart B. Postoperative neuropsychological dysfunction and cerebral oxygenation during cardiac surgery.  Thorac Cardiovasc Surg.. 1995;  43 260-264
• 9 Cooper C, Sharpe M, Elwell C, Springett R, Penrice J, Tyszczuk L, Amess P, Wyatt J, Quaresima V, Delpy D. The cytochrome oxidase redox state in vivo.  Adv Exp Med Biol. 1997;  428 449-456
• 10 Cooper C E, Cope M, Quaresima V, Ferrari M, Nemoto E, Springett R, Matcher S, Amess P, Penrice J, Tyszczuk L, Wyatt J, Delpy D T. Measurement of cytochrome oxidase redox state by near infrared spectroscopy.  Adv Exp Med Biol. 1997;  413 63-73
• 11 Cooper C E, Cope M, Springett R, Amess P N, Penrice J, Tyszczuk L, Punwani S, Ordidge R, Wyatt J, Delpy D T. Use of mitochondhal inhibitors to demonstrate that cytochrome oxidase near-infrared spectroscopy can measure mitochondrial dysfunction noninvasively in the brain.  J Cereb Blood Flow Metab. 1999;  19 27-38
• 12 Cooper C E, Delpy D T, Nemoto E M. The relationship of oxygen delivery to absolute haemoglobin oxygenation and mitochondrial cytochrome oxidase redox state in the adult brain: a near-infrared spectroscopy study.  Biochem J. 1998;  332 627-632