Intermittent Hypoxia and the Practice of Anesthesia

Department of Anesthesia, McGill University Health Centre, Montreal, Canada.
Anesthesiology (Impact Factor: 5.88). 05/2009; 110(4):922-7. DOI: 10.1097/ALN.0b013e31819c480a
Source: PubMed


Intermittent hypoxia, a powerful and unique stimulus, leads to physiologic changes that are distinct from those associated with either single or continuous hypoxic exposure. There is an accumulating body of evidence that the neurocognitive, inflammatory and cardiovascular symptoms that characterize the syndrome of obstructive sleep apnea are linked to the stimulus of intermittent hypoxia. In addition, altered sensitivities to opiates in children with obstructive sleep apnea have been linked to recurrent hypoxia during sleep. Therefore anesthesiologists should have an understanding of this important stimulus.

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    • "Furthermore, both children suffering from OSA [63] and rats treated during development with chronic intermittent hypoxia [64] were more sensitive to the respiratory depressant effect of fentanyl. Although the mechanism for this effect of recurrent hypoxia on pain and analgesia systems is vague, in vivo evidence suggests that an up-regulation of μ-opioid receptors might be responsible for the observed increase in the potency of opioids [65]–[67]. "
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    ABSTRACT: Obstructive sleep apnea (OSA) is characterized by recurrent nocturnal hypoxia and sleep disruption. Sleep fragmentation caused hyperalgesia in volunteers, while nocturnal hypoxemia enhanced morphine analgesic potency in children with OSA. This evidence directly relates to surgical OSA patients who are at risk for airway compromise due to postoperative use of opioids. Using accepted experimental pain models, we characterized pain processing and opioid analgesia in male volunteers recruited based on their risk for OSA. After approval from the Intitutional Review Board and informed consent, we assessed heat and cold pain thresholds and tolerances in volunteers after overnight polysomnography (PSG). Three pro-inflammatory and 3 hypoxia markers were determined in the serum. Pain tests were performed at baseline, placebo, and two effect site concentrations of remifentanil (1 and 2 µg/ml), an μ-opioid agonist. Linear mixed effects regression models were employed to evaluate the association of 3 PSG descriptors [wake after sleep onset, number of sleep stage shifts, and lowest oxyhemoglobin saturation (SaO(2)) during sleep] and all serum markers with pain thresholds and tolerances at baseline, as well as their changes under remifentanil. Forty-three volunteers (12 normal and 31 with a PSG-based diagnosis of OSA) were included in the analysis. The lower nadir SaO(2) and higher insulin growth factor binding protein-1 (IGFBP-1) were associated with higher analgesic sensitivity to remifentanil (SaO(2), P = 0.0440; IGFBP-1, P = 0.0013). Other pro-inflammatory mediators like interleukin-1β and tumor necrosis factor-α (TNF-α) were associated with an enhanced sensitivity to the opioid analgesic effect (IL-1β, P = 0.0218; TNF-α, P = 0.0276). Nocturnal hypoxemia in subjects at high risk for OSA was associated with an increased potency of opioid analgesia. A serum hypoxia marker (IGFBP-1) was associated with hypoalgesia and increased potency to opioid analgesia; other pro-inflammatory mediators also predicted an enhanced opioid potency. CLINICALTRIALS.GOV NCT00672737.
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    ABSTRACT: To investigate the effect of altitude on perioperative opioid requirements in otherwise healthy children. To investigate whether children living and having surgery at high altitude received different doses of fentanyl than those living and having surgery at sea level. Recent studies in animals (Anesthesiology, 105, 2006 and 715) and children with obstructive sleep apnea (Anesthesiology, 105, 2006 and 665; Anesthesiology 100, 2004 and 806) suggest that analgesic effects of exogenous opioids are enhanced by hypoxia. However, the effects of hypoxia on perioperative narcotic requirements in otherwise healthy children have not been previously reported. We reviewed retrospectively the opioid requirements of pediatric patients who underwent cleft lip or palate surgery during Smile Network International mission trips to Cusco and Lima, Peru between 2007 and 2009. Patients who had surgery at high altitude were compared to those who had surgery at sea level. All patients received a standardized anesthetic with intravenous fentanyl as the only perioperative opioid. Hundred and two patients had surgery at 3399 m above sea level (masl) (Cusco) and 169 patients had surgery at 150 masl (Lima). Patients at high altitude had significantly lower baseline oxygen saturations (92 ± 4% vs 98 ± 3%; P < 0.001) and received 40% less opioid (1.2 ± 0.8 vs 2.0 ± 1.4 μg·kg(-1) per h; P < 0.001) compared to patients at sea level. Opioid administration was reduced in otherwise healthy children with altitude-induced chronic hypoxia when compared to non-hypoxic children undergoing similar operations under similar anesthetic regimens. Whether this difference is due to altitude or altitude-induced hypoxia, requires further study.
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