Hypoxia, hypercarbia, and mortality reporting in studies of anaesthesia-related neonatal neurodevelopmental delay in rodent models: A systematic review.

BACKGROUND: The concept of anaesthesia-related neonatal neurotoxicity originated in neonatal rodent models, yet prospective clinical studies have largely not supported this concern. OBJECTIVES: To determine the frequency and magnitude of hypercarbia, hypoxia and death in rodent models of neonatal anaesthetic toxicity and neurodevelopmental delay. DESIGN: Systematic review of published rodent studies of neonatal anaesthesia neurotoxicity. We documented anaesthetic, route, dose, frequency and duration of exposures. We further report ventilation method, documentation of adequacy of ventilation [arterial blood gas (ABG), other], mortality and the reporting of mortality. DATA SOURCES: A PubMed literature search from 2003 to 2017 was conducted to identify studies on neurotoxicity in neonatal rodent models. ELIGIBILITY: Studies were included when at least one group of animals fell within the postnatal age range of 3 to 15 days. Only English language original studies published as full-length articles in peer reviewed journals were included in the final analysis. RESULTS: One hundred and three manuscripts were included. Ninety-eight percent of studies were conducted using spontaneous ventilation (101/103), with ABG monitoring used in only 33% of studies and visual monitoring alone for respiratory distress or cyanosis was employed in 60%. Of the 33% who reported ABG results, there were widely divergent values, with most reporting modest-to-severe hypercarbia. Mortality (median 11%, range of 0 to 40%), which infers severe hypoxia, was documented in only 36/103 (35%) reports. CONCLUSION: Hypoxia and hypercarbia have known apoptotic effects on developing brains. Hence, the inadequate control of hypercarbia and hypoxia in neonatal rodent models of anaesthetic exposure during spontaneous ventilation suggests that the evidence for developmental delay and neurotoxicity attributed to anaesthesia may not be valid in humans.

Comparison of passive leg raising and hyperemia on macrovascular and microvascular responses.

Passive leg raising is a simple diagnostic maneuver that has been proposed as a measure of arterial vasodilator reserve and possibly endothelial function. While passive leg raising has previously been shown to lower blood pressure, increase flow velocity and cause brachial artery dilation, its effects on microvascular flow has not been well studied. Also, passive leg raising has been directly compared previously to upper arm but never to lower arm occlusion of blood flow induced hyperemia responses. We compared changes in macrovascular indices measured by brachial artery ultrasound and microvascular perfusion measured by Laser Doppler Flowmetry induced by passive leg raising to those provoked by upper arm and lower arm induced hyperemia in healthy subjects. Upper arm induced hyperemia increased mean flow velocity by 398%, induced brachial artery dilatation by 16.3%, and increased microvascular perfusion by 246% (p<.05 for all). Lower arm induced hyperemia increased flow velocity by 227%, induced brachial artery dilatation by 10.8%, and increased microvascular perfusion by 281%. Passive leg raising increased flow velocity by 29% and brachial artery dilatation by 5.6% (p<.05 for all), but did not change microvascular perfusion (-5%, p=ns). In conclusion, passive leg raising increases flow velocity orders of magnitude less than does upper arm or lower arm induced hyperemia. Passive leg raising-induced brachial artery dilatation is less robust than either of these hyperemic techniques. Finally, although upper arm and lower arm hyperemia elicits macrovascular and microvascular responses, passive leg raising elicits only macrovascular responses.

Transcutaneous CO2 versus end-tidal CO2 in neonates and infants undergoing surgery: a prospective study.

Aim: End-tidal CO2 (EtCO2) is the standard in operative care along with pulse oximetry for ventilation assessment. It is known to be less accurate in the infant population than in adults. Many neonatal intensive care units (NICU) have converted to utilizing transcutaneous CO2 (tcPCO2) monitoring. This study aimed to compare perioperative EtCO2 to tcPCO2 in the pediatric perioperative population specifically below 10 kg, which encompasses neonates and some infants. Methods: After IRB approval and parental written informed consent, we enrolled neonates and infants weighing less than 10 kg, who were scheduled for elective surgery with endotracheal tube under general anesthesia. PCO2 was monitored with EtCO2 and with tcPCO2. Venous blood gas (PvCO2) samples were drawn at the end of the anesthetic. We calculated a mean difference of EtCO2 minus PvCO2 (Delta EtCO2), and tcPCO2 minus PvCO2 (Delta tcPCO2) from end-of-case measurements. The mean differences in the NICU and non-NICU patients were compared by t-tests and Bland-Altman analysis. Results: Median age was 10.9 weeks, and median weight was 4.4 kg. NICU (n=6) and non-NICU (n=14) patients did not differ in PvCO2. Relative to the PvCO2, the Delta EtCO2 was much greater in the NICU compared to the non-NICU patients (-28.1 versus -9.8, t=3.912, 18 df, P=0.001). Delta tcPCO2 was close to zero in both groups. Although both measures obtained simultaneously in the same patients agreed moderately with each other (r =0.444, 18 df, P=0.05), Bland-Altman plots indicated that the mean difference (bias) in EtCO2 measurements differed significantly from zero (P<0.05). Conclusions: EtCO2 underestimates PvCO2 values in neonates and infants under general anesthesia. TcPCO2 closely approximates venous blood gas values, in both the NICU and non-NICU samples. We, therefore, conclude that tcPCO2 is a more accurate measure of operative PvCO2 in infants, especially in NICU patients.