Naloxone is a non-selective, short-acting opioid receptor antagonist that has a long clinical history of successful use and is presently considered a safe drug over a wide dose range (up to 10 mg). In opioid-dependent patients, naloxone is used in the treatment of opioid-overdose-induced respiratory depression, in (ultra)rapid detoxification and in combination with buprenorphine for maintenance therapy (to prevent intravenous abuse). Risks related to naloxone use in opioid-dependent patients are: i) the induction of an acute withdrawal syndrome (the occurrence of vomiting and aspiration is potentially life threatening); ii) the effect of naloxone may wear off prematurely when used for treatment of opioid-induced respiratory depression; and iii) in patients treated for severe pain with an opioid, high-dose naloxone and/or rapidly infused naloxone may cause catecholamine release and consequently pulmonary edema and cardiac arrhythmias. These risks warrant the cautious use of naloxone and adequate monitoring of the cardiorespiratory status of the patient after naloxone administration where indicated.

This cohort study uses nationwide data to determine opioid prescription patterns and survey data to examine risk factors associated with opioid prescription in the Netherlands.

Monitors that estimate nociception during anesthesia may be used to guide opioid and other analgesics administration to optimize anesthesia care and possibly outcome. We reviewed the literature to evaluate current evidence of the effect of nociception-guided management over standard anesthesia practice during surgery. A systematic review of the literature on the effect of nociception monitoring on anesthesia practice was conducted. Reports were eligible if they compared nociception-guided anesthesia to standard practice during surgery. Primary endpoint of this review is intraoperative opioid consumption. Secondary endpoints included hemodynamic control, postoperative pain and pain treatment. We identified 12 randomized controlled trials that compared one of five different nociception monitoring techniques to standard anesthesia care. Most studies were single center studies of small sample size. Six studies reported intraoperative opioid consumption as primary outcome. There was considerable variability with respect to surgical procedure and anesthesia technique. For nociception monitors that were investigated by more than one study, analysis of the pooled data was performed. The surgical plethysmographic index was the only monitor for which an intra operative opioid sparing effect was found. For the other monitors, either no effect was detected, or pooled analysis could not be performed due to paucity of study data. On secondary outcomes, no consistent effect of nociception-guided anesthesia could be established. Although some nociception monitors show promising results, no definitive conclusions regarding the effect of nociception monitoring on intraoperative opioid consumption or other anesthesia related outcome can be drawn. Clinical trial number PROSPERO ID 102913.

ϩ ions and CO2 on hypoxic sensitivity in humans. We also examined whether hypoxic sensitivity, conventionally defined as the ratio of (hypoxic Ϫ normoxic) ventilation over (hypoxic Ϫ normoxic) Hb oxygen saturation can also be estimated by taking the ratio (hypoxic Ϫ normoxic) ventilation over (logPa O 2 hypoxia Ϫ logPa O 2 normoxia), enabling one to measure the hypoxic response independently from potential confounding influences of changes in position of the Hb oxygen saturation curve. We used acetazolamide to induce a metabolic acidosis. To determine the acute hypoxic response (AHR), we performed step decreases in end-tidal PO2 to ϳ50 Torr lasting 5 min each at three different constant end-tidal PCO2 levels. Nine subjects ingested 250 mg of acetazolamide or placebo every 8 h for 3 days in a randomized double-blind crossover design. The metabolic acidosis was accompanied by a rise in ventilation, a substantial fall in Pa CO 2 , and a parallel leftward shift of the ventilatory CO 2 response curve. In placebo, CO2 induced equal relative increases in hypoxic sensitivity (O 2-CO2 interaction) regardless of the way it was defined. Acetazolamide shifted the response line representing the relationship between hypoxic sensitivity and arteriala without altering its slope, indicating that it did not affect the O2-CO2 interaction. So, in contrast to an earlier belief, CO2 and H ϩ have separate effects on hypoxic sensitivity. This was also supported by the finding that infusion of bicarbonate caused a leftward shift of the hypoxic sensitivity-[H ϩ ]a response lines in placebo and acetazolamide. A specific inhibitory effect of acetazolamide on hypoxic sensitivity was not demonstrated. hypoxic sensitivity; O2-CO2 interaction; hydrogen ions; CO2 THE HYPOXIC VENTILATORY RESPONSE in humans is biphasic and consists of an initial rise in ventilation initiated by the carotid bodies followed by a secondary roll-off, usually designated as hypoxic ventilatory decline (HVD) (8,13,16,25). The magnitude of this decline is proportionally related to the initial rise in ventilation in response to acute hypoxia and thus also to the intensity of the hypoxic stimulus (8,18,25). Measurement of the ventilatory response to hypoxia without the "confounding" influence of HVD is possible by exposing subjects to brief step-wise changes in end-tidal PO 2 lasting 3-5 min, a period too short for HVD to develop. Consequently, the ventilatory response to such an acute hypoxic challenge (the acute hypoxic response, AHR) is attributed to the peripheral chemoreceptors in the carotid bodies. The magnitude of the AHR can be influenced by many factors such as the background arterial PCO 2 . A rise in Pa CO 2 augments the AHR, and this is known as multiplicative O 2 -CO 2 interaction (6, 7, 10). This phenomenon is thought to reside in the carotid bodies (15,22,26), but its mechanism at the molecular level in oxygen-sensitive type I cells remains to be elucidated (29). A rise in Pa CO 2 not only leads to extracellular acidosis (acidemia) but also to increases in ...

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