Key result
The combination of alfentanil and sevoflurane caused synergistic depression of resting ventilation and heart rate, while their effects on hypoxic responses and Bispectral Index were additive.
Why the study?
Does the combined administration of sevoflurane and alfentanil synergistically depress cardiorespiratory control and Bispectral Index in healthy volunteers?
Does the combined administration of sevoflurane and alfentanil synergistically depress cardiorespiratory control and Bispectral Index in healthy volunteers?
The combination of alfentanil and sevoflurane causes synergistic depression of resting ventilation and heart rate, but additive depression of hypoxic responses and BIS.
May warrant caution with combined use; leaves open translation to patients with comorbidities.
BACKGROUND: Respiratory depression is a serious side effect of anesthetics and opioids. The authors examined the influence of the combined administration of sevoflurane and alfentanil on ventilatory control, heart rate (HR), and Bispectral Index (BIS) in healthy volunteers. METHODS: Step decreases in end-tidal partial pressure of oxygen from normoxia into hypoxia (approximately 50 mmHg) at constant end-tidal partial pressure of carbon dioxide (approximately 48 mmHg) were performed in nine male volunteers at various concentrations of alfentanil and sevoflurane, ranging from 0 to 50 ng/ml for alfentanil and from 0 to 0.4 end-tidal concentration (ET%) for sevoflurane, and with various combinations of alfentanil and sevoflurane. The alfentanil-sevoflurane interactions on normoxic resting (hypercapnic) ventilation (Vi), HR, hypoxic Vi, and HR responses and BIS were assessed by construction of response surfaces that related alfentanil and sevoflurane to effect using a population analysis. RESULTS: Concentration-effect relations were linear for alfentanil and sevoflurane. Synergistic interactions were observed for resting Vi and resting HR. Depression of Vi by 25% occurred at 38 +/- 11 ng/ml alfentanil (population mean +/- SE) and at 0.7 +/- 0.4 ET% sevoflurane. One possibility for 25% reduction when alfentanil and sevoflurane are combined is 13.4 ng/ml alfentanil plus 0.12 ET% sevoflurane. Additive interactions were observed for hypoxic Vi and HR responses and BIS. Depression of the hypoxic Vi response by 25% occurred at 16 +/- 1 ng/ml alfentanil and 0.14 +/- 0.05 ET% sevoflurane. The effect of sevoflurane on the BIS (25% reduction of BIS occurred at 0.45 +/- 0.08 ET%) was independent of the alfentanil concentration. CONCLUSIONS: Response surface modeling was used successfully to analyze the effect of interactions between two drugs on respiration. The combination of alfentanil and sevoflurane causes more depression of Vi and HR than does the summed effect of each drug administered separately. The effects of combining alfentanil and sevoflurane on hypoxic Vi and HR responses and BIS could be predicted from the separate dose-response curves. Over the dose range tested, the hypoxic response is more sensitive to the effects of anesthetics and opioids relative to resting ventilation.
No takes yet. Share an insight, caveat, or question.
Dahan et al. (2001) studied Healthy volunteers (n=9). Combined administration of sevoflurane and alfentanil vs. Separate administration of each drug was evaluated on Ventilatory control, heart rate, and Bispectral Index. The combination of alfentanil and sevoflurane caused synergistic depression of resting ventilation and heart rate, while their effects on hypoxic responses and Bispectral Index were additive.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: