The effects of intraoperative hypotension on neurodevelopment: Much ado about nothing?
Michael E. Nemergut MD PhD and Stephen J. Gleich MD
Over the past couple of days, I’ve highlighted several articles on intraoperative hypotension, really in preparation for today’s PAAD. Today we’ll be reviewing a paper by Ing et al[1] from Columbia University. Caleb is one of the foremost researchers in neuro developmental outcomes following general anesthesia in the very young and I pay special attention to his work for the PAAD readership. After reading today’s article a couple of times I was afraid that I was missing something, so I asked one of my former fellows and mentees, Dr. Mike Nemergut of the Mayo Clinic, to review it. Mike asked one of his collagues and mentees, Dr. Stephen Gleich, to assist. The circle remains unbroken. Myron Yaster MD
Original article
Ing C, DeStephano D, Hu T, Reighard C, Lackraj D, Geneslaw AS, Miles CH, Kim M. Intraoperative Blood Pressure and Long-Term Neurodevelopmental Function in Children Undergoing Ambulatory Surgery. Anesth Analg. 2022 Oct 1;135(4):787-797. PMID: 36108191
Anesthesiologists have long championed patient safety efforts. As anesthetics do not directly solve basic medical problems (for example, appendicitis), it can be argued that our primary offering to patients is risk, and how one modulates that risk defines the aptitude of an individual provider. Thought of in this light, the preponderance of patient safety research coming from departments of anesthesiology is not at all surprising. Furthermore, the potential harms of anesthetics strike a particular chord with anesthesiologists and such potentialities are rigorously researched and reported.
While the potential impact of anesthetics on pediatric brain development has had a particular place in this legacy over the past decade, more recent concern has developed from data reporting the association between intraoperative hypotension and negative myocardial,[2] renal,[3] and neurologic outcomes.[4] Indeed, some researchers have argued that data supporting pediatric anesthetic neurotoxicity may be explained by deficits in anesthetic management, including hypotension, rather than an intrinsic effect of the anesthetics themselves.[5] As such, Ing and colleagues sought to study the relationship between intraoperative hypotension and outcome.[1]
This single-center, retrospective study evaluated the association of children having a single, ambulatory surgical procedure and subsequent neurological function. Children having multiple surgical procedures, chronic medical conditions, as well as pre-existing mental conditions were excluded. The intraoperative data of these children were evaluated, and a single, time-weighted average mean arterial blood pressure (MAP) was calculated for each anesthetic record. After stratifying by age and sex, the mean MAP was used to assign patients to five separate intraoperative MAP groups (very low, low, reference, high, and very high). These children were subsequently evaluated for the presence of a mental condition, defined by a billing claim for any ICD-9 or ICD-10 mental illness from the time of surgery till censoring (the last available billing claim for each child). Over 14,700 children were included for analysis and no statistically significant differences in the risk of mental disorder diagnosis was found based on the predetermined intraoperative MAP categories. In secondary analysis, the authors evaluated intraoperative MAP as a continuous variable and found that each decile increase in mean intraoperative MAP was associated with a hazard ratio of 0.965 for subsequent mental disorder diagnosis, translating to an average decrease of ~3.5% for every decile increase in MAP.
We submit that Ing and colleagues are to be congratulated for the meticulous nature of their retrospective analysis, comprehensive attempts to identify confounding variables, as well as honest reporting of the limitations of their study. We applaud such studies for their attempt to identify basic, modifiable factors that may impact the care we provide children daily. We nevertheless would like to highlight some of these limitations for the benefit of the reader. It is noteworthy that, while the median time to follow-up up was 120 days, almost a fourth of all patients had no follow-up after surgery at all and another fourth had follow-up within 7 days. Such a high percentage having no or rapid follow-up may greatly impair the ability to capture a mental disorder. In addition, while data are very limited as to what the normal range for intraoperative blood pressure is for children, it is noteworthy that the separation of mean intraoperative MAP groups was often quite narrow, sometimes only ~2 mmHg. These ranges may be less than the accuracy of commonly used ocillometric MAP measurement devices, which have reported acceptable accuracy of 5 mmHg with a standard deviation of 8 mmHg.[6]
This may further be further compounded by the fact the anatomic site of MAP measurement was not noted and can differ dramatically dependent upon measurement site. For example, in children less than 4 years old, an oscillometric MAP measured in the leg may be 10 mmHg lower compared to the arm.[7, 8] Lastly, the hazard ratio decrement noted with hypertension appears weak, notably less than other hazard ratios that are widely held in clinical practice (such as the association between salicylates and Reye syndrome).[9] Trying to “fix” hypotension may also cause problems too like fluid overload, inadequate anesthesia, inappropriate use of vasoactive pressors, etc. Thus, while we applaud the authors for evaluating this important issue, we find ourselves neither reassured by the relative benignity of hypotension nor the reported protection from hypertension. Hopefully, this will spur future prospective studies to evaluate this important issue. In the meantime, in the absence of further data, we remain defenders of normotension.
References:
1. Ing, C., et al., Intraoperative Blood Pressure and Long-Term Neurodevelopmental Function in Children Undergoing Ambulatory Surgery. Anesth Analg, 2022. 135(4): p. 787-797.
2. van Waes, J.A., et al., Association between Intraoperative Hypotension and Myocardial Injury after Vascular Surgery. Anesthesiology, 2016. 124(1): p. 35-44.
3. Sun, L.Y., et al., Association of intraoperative hypotension with acute kidney injury after elective noncardiac surgery. Anesthesiology, 2015. 123(3): p. 515-23.
4. Maheshwari, K., et al., Association Between Perioperative Hypotension and Delirium in Postoperative Critically Ill Patients: A Retrospective Cohort Analysis. Anesth Analg, 2020. 130(3): p. 636-643.
5. Hansen, T.G. and P.A. Lönnqvist, The rise and fall of anaesthesia-related neurotoxicity and the immature developing human brain. Acta Anaesthesiol Scand, 2016. 60(3): p. 280-3.
6. Healthcare, G. Dinamap ProCare Vital Signs Monitor. 10/26/2022]; Available from: https://www.cardiacdirect.com/brochures/MedicalDINAMAP420VitalSignsMonitorspecifications.pdf.
7. Short, J.A., Noninvasive blood pressure measurement in the upper and lower limbs of anaesthetized children. Paediatr Anaesth, 2000. 10(6): p. 591-3.
8. Keidan, I., et al., Inconsistency between simultaneous blood pressure measurements in the arm, forearm, and leg in anesthetized children. J Clin Anesth, 2014. 26(1): p. 52-7.
9. Nemergut, M.E., D. Aganga, and R.P. Flick, Anesthetic neurotoxicity: what to tell the parents? Paediatr Anaesth, 2014. 24(1): p. 120-6.