Justin Skowno

Exercising with reserve: evidence that the central nervous system regulates prolonged exercise performance

Objective: The purpose of this study was to measure the effects of an amphetamine (methylphenidate) on exercise performance at a fixed rating of perceived exertion of 16. Methods: Eight elite cyclists ingested 10 mg methylphenidate in a randomised, placebo-controlled crossover trial. Results: Compared with placebo, subjects receiving methylphenidate cycled for approximately 32% longer before power output fell to 70% of the starting value. At the equivalent time at which the placebo trial terminated, subjects receiving methylphenidate had significantly higher power outputs, oxygen consumptions, heart rates, ventilatory volumes and blood lactate concentrations although electromyographic activity remained unchanged. The ingestion of a centrally acting stimulant thus allowed subjects to exercise for longer at higher cardiorespiratory and metabolic stress indicating the presence of a muscular reserve in the natural state. Conclusions: This suggests that endurance performance is not only “limited” by mechanical failure of the exercising muscles (“peripheral fatigue”). Rather performance during prolonged endurance exercise under normal conditions is highly regulated by the central nervous system to ensure that whole-body homeostasis is protected and an emergency reserve is always present.

New technologies in pediatric anesthesia

This article reviews potential pediatric applications of 3 new technologies. (1) Pulse oximetry‐based hemoglobin determination: Hemoglobin determination using spectrophotometric methods recently has been introduced in adults with varied success. This non‐invasive and continuous technology may avoid venipuncture and unnecessary transfusion in children undergoing surgery with major blood loss, premature infants undergoing unexpected and complicated emergency surgery, and children with chronic illness. (2) Continuous cardiac output monitoring: In adults, advanced hemodynamic monitoring such as continuous cardiac output monitoring has been associated with better surgical outcomes. Although it remains unknown whether similar results are applicable to children, current technology enables the monitoring of cardiac output non‐invasively and continuously in pediatric patients. It may be important to integrate the data about cardiac output with other information to facilitate therapeutic interventions. (3) Anesthesia information management systems: Although perioperative electronic anesthesia information management systems are gaining popularity in operating rooms, their potential functions may not be fully appreciated. With advances in information technology, anesthesia information management systems may facilitate bedside clinical decisions, administrative needs, and research in the perioperative setting.

Feasibility of cerebral near-infrared spectroscopy monitoring in the pre-hospital environment.

Traumatic brain injury (TBI) is a significant cause of death and severe disability from trauma. Pre‐hospital care of patients with TBI may be aided by non‐invasive monitoring of cerebral tissue oxygenation. This pilot observational study was designed to assess if cerebral tissue oximetry using near‐infrared spectroscopy (NIRS) is feasible in the pre‐hospital and transport environment.

Cerebral oxygen saturation and tissue hemoglobin concentration as predictive markers of early postoperative outcomes after pediatric cardiac surgery

Near‐infrared spectroscopy (NIRS) provides an assessment of cerebral oxygenation and tissue hemoglobin concentration.

Evidence of cardiac functional reserve upon exhaustion during incremental exercise to determine VO2max

Background There remains considerable debate regarding the limiting factor(s) for maximal oxygen uptake (VO2max). Previous studies have shown that the central circulation may be the primary limiting factor for VO2max and that cardiac work increases beyond VO2max. Aim We sought to evaluate whether the work of the heart limits VO2max during upright incremental cycle exercise to exhaustion. Methods Eight trained men completed two incremental exercise trials, each terminating with exercise at two different rates of work eliciting VO2max (MAX and SUPRAMAX). During each exercise trial we continuously recorded cardiac output using pulse-contour analysis calibrated with a lithium dilution method. Intra-arterial pressure was recorded from the radial artery while pulmonary gas exchange was measured continuously for an assessment of oxygen uptake. Results The workload during SUPRAMAX (mean±SD: 346.5±43.2 W) was 10% greater than that achieved during MAX (315±39.3 W). There was no significant difference between MAX and SUPRAMAX for Q (28.7 vs 29.4 L/min) or VO2 (4.3 vs 4.3 L/min). Mean arterial pressure was significantly higher during SUPRAMAX, corresponding to a higher cardiac power output (8.1 vs 8.5 W; p<0.06). Conclusions Despite similar VO2 and Q, the greater cardiac work during SUPRAMAX supports the view that the heart is working submaximally at exhaustion during an incremental exercise test (MAX).

The impact of general anesthesia on child development and school performance: a population‐based study

There has been considerable interest in the possible adverse neurocognitive effects of exposure to general anesthesia and surgery in early childhood.

An International, Multicenter, Observational Study of Cerebral Oxygenation during Infant and Neonatal Anesthesia

Background: General anesthesia during infancy is associated with neurocognitive abnormalities. Potential mechanisms include anesthetic neurotoxicity, surgical disease, and cerebral hypoxia–ischemia. This study aimed to determine the incidence of low cerebral oxygenation and associated factors during general anesthesia in infants. Methods: This multicenter study enrolled 453 infants aged less than 6 months having general anesthesia for 30 min or more. Regional cerebral oxygenation was measured by near-infrared spectroscopy. We defined events (more than 3 min) for low cerebral oxygenation as mild (60 to 69% or 11 to 20% below baseline), moderate (50 to 59% or 21 to 30% below baseline), or severe (less than 50% or more than 30% below baseline); for low mean arterial pressure as mild (36 to 45 mmHg), moderate (26 to 35 mmHg), or severe (less than 25 mmHg); and low pulse oximetry saturation as mild (80 to 89%), moderate (70 to 79%), or severe (less than 70%). Results: The incidences of mild, moderate, and severe low cerebral oxygenation were 43%, 11%, and 2%, respectively; mild, moderate, and severe low mean arterial pressure were 62%, 36%, and 13%, respectively; and mild, moderate, and severe low arterial saturation were 15%, 4%, and 2%, respectively. Severe low oxygen saturation measured by pulse oximetry was associated with mild and moderate cerebral desaturation; American Society of Anesthesiology Physical Status III or IV versus I was associated with moderate cerebral desaturation. Severe low cerebral saturation events were too infrequent to analyze. Conclusions: Mild and moderate low cerebral saturation occurred frequently, whereas severe low cerebral saturation was uncommon. Low mean arterial pressure was common and not well associated with low cerebral saturation. Unrecognized severe desaturation lasting 3 min or longer in infants seems unlikely to explain the subsequent development of neurocognitive abnormalities.

Using a pulse oximeter to determine clinical depth of anesthesia-investigation of the utility of the perfusion index.

Peripheral vasodilation is a well‐recognized side effect of general anesthesia, and induces changes in the amplitude of the pulse plethysmograph (PPG) waveform. This can be continuously quantitaed using the Perfusion Index (PI), a ratio of the pulsatile to nonpulsatile signal amplitude in the PPG waveform. We hypothesized that the perfusion index would rise with the induction of anesthesia in children, and fall with emergence, and performed a prospective, observational study to test this.

Staying away from the edge - cerebral oximetry guiding blood pressure management.

Neurological outcome after anesthesia and surgery in young infants has always been of interest, including hypoxia-ischemia, cardiac arrest, embolic stroke, and more recently, ‘neurotoxicity.’ While ‘neurotoxicity’ grabs the headlines, cerebral oxygenation and perfusion changes associated with anesthesia may also be a contributing factor to the neurological outcome. In this issue, Michelet et al. describe the association between blood pressure changes in infants <3 months of age having anesthesia, and changes in regional cerebral oxygen saturation (rScO2) using Near Infrared Spectroscopy (NIRS). Their study demonstrates that cerebral desaturation occurs in <10% of patients whose systolic blood pressure decline is <20% from baseline, and more than 90% whose blood pressure decline is more than 35%. Of their 60 patients, 14 (23%) demonstrated reductions of rScO2 of >20%. The authors conclude by saying that ‘maintaining systolic blood pressure within 20% of baseline values appears a valid clinical target’. An important issue is the definition of what constitutes cerebral desaturation, >20% below baseline rScO2 being the criteria used by Michelet et al. There is very little data to support any one definition in infants, in the absence of large-scale trials with long-term neurodevelopmental follow-up. Studies in piglets by Kurth et al. (1) indicated cerebral hypoxia-ischemia rScO2 thresholds of between 33% and 44%. Thus, off a baseline rScO2 of 75%, a drop of 20% still leaves a buffer before damage is likely to occur, while being large enough to eliminate monitor-based fluctuations and normal physiological variation as the cause of the drop. Another important issue is the patient population and monitoring by Michelet et al. The patients were not healthy, elective surgery patients. Almost all were at risk of pulmonary aspiration and consequently received rapid sequence induction. rScO2 values were excluded if SpO2 was <95%. Thus, cerebral desaturation might have been under reported as arterial desaturation causes cerebral desaturation. During the anesthetic, arterial pressure was monitored every 10 min, far less frequently than the 3-min standard in many countries. Thus, cerebral desaturation might have been over observed because hypotension could have been more severe from delayed treatment from infrequent arterial pressure monitoring. Is cerebral desaturation detected by NIRS linked to neurological damage in humans? The emerging answer from the pediatric cardiac surgical literature suggests the answer is a qualified yes (2), although the multitude of differences in patient and procedural risk factors and the actual cerebral saturations involved may add to this uncertainty. A ‘dose–response’ relationship must exist, with more significant desaturation, for a longer period, being associated with more neuronal damage. Researchers in this area will need to cater for both desaturation and duration, as has been recently defined and reported in a clinical trial in neonatal ICU patients (3). Up until relatively recently, the observation that ‘the infant woke up fine after my anesthetic’, has been the standard by which we have assessed neurocognitive outcomes. As we have learned that neurocognitive deficits and developmental delay are often subtle and may not manifest until school age, this offhanded qualitative approach to conclude safety and no untoward complications does not suffice today. Unfortunately not all infants do wake up fine, and low blood pressure has been implicated in the etiology of postoperative encephalopathies in six neonates (4). In less obvious cases of neurological deficit, it is not detected early on after the procedure, but may then contribute to the putative association between anesthesia and long-term neurocognitive and behavioral deficits. We have all seen substantial drops in arterial blood pressure in our patients, to which we have variably reacted, the primary question being ‘what should we aim for’. We justify our more relaxed definition of hypotension and treatment in part by referencing the reduction in cerebral metabolic rate due to anesthesia, anesthetic-related hypothermia, and our experience that the infant ‘wakes up fine’. The neuroprotection from anesthesia and mild hypothermia somehow ‘balance out’ the possibility of cerebral ischemia from hypotension. They may, but in the absence of any attempt to actually measure cerebral variables, they also may not. Cerebral perfusion and neuroprotection are affected by multiple variables in addition to blood pressure, and over-focussing on blood pressure changes may obscure other important interactions, such as cerebral oxygenation and anesthetic depth. Interpretation of the multiple variables influencing cerebral blood flow is complex, and the use of a multidimensional monitor such as NIRS may facilitate the process (5), although caution is again warranted when trying to infer the status of cerebral blood flow and autoregulation using indirect means.

Measurement of cardiac output during exercise in healthy, trained humans using lithium dilution and pulse contour analysis

The aim of this study was to evaluate the use of pulse contour analysis calibrated with lithium dilution in a single device (LiDCO) for measurement of cardiac output (Q) during exercise in healthy volunteers. We sought to; (a) compare pulse contour analysis (PulseCO) and lithium indicator dilution (LiDCO) for the measurement of Q during exercise, and (b) assess the requirement for recalibration of PulseCO with LiDCO during exercise. Ten trained males performed multi-stage cycling exercise at intensities below and above ventilatory threshold before constant load maximal exercise to exhaustion. Uncalibrated PulseCO Q (Qraw) was compared to that calibrated with lithium dilution at baseline Qbaseline, during submaximal exercise below (Qlow) and above (Qhigh) ventilatory threshold, and at each exercise stage individually (Qexercise). There was a significant difference between Qbaseline and all other calibration methods during exercise, but not at rest. No significant differences were observed between other methods. Closest agreement with Qexercise was observed for Qhigh (bias ± limits of agreement: 4.8 ± 30.0%). The difference between Qexercise and both Qlow and Qraw was characterized by low bias (4-7%) and wide limits of agreement (> ± 40%). Calibration of pulse contour analysis with lithium dilution prior to exercise leads to a systematic overestimation of exercising cardiac output. A single calibration performed during exercise above the ventilatory threshold provided acceptable limits of agreement with an approach incorporating multiple calibrations throughout exercise. Pulse contour analysis may be used for Q measurement during exercise providing the system is calibrated during exercise.