Frequency of low minute ventilation events as indication of post-operative respiratory depression

2017 ◽  
Author(s):  
Turan Alparslan
Keyword(s):  
Respiratory Depression ◽  
Minute Ventilation

scholarly journals Multi-Level Regulation of Opioid-Induced Respiratory Depression

Physiology ◽  
2020 ◽  
Vol 35 (6) ◽  
pp. 391-404
Author(s):  
Barbara Palkovic ◽  
Vitaliy Marchenko ◽  
Edward J. Zuperku ◽  
Eckehard A. E. Stuth ◽  
Astrid G. Stucke
Keyword(s):  
Respiratory Rate ◽  
Respiratory Depression ◽  
Minute Ventilation ◽  
Direct Effects ◽  
Respiratory Phase ◽  
Multi Level ◽  
Prebotzinger Complex ◽  
Prebötzinger Complex ◽  
Excitatory Drive

Opioids depress minute ventilation primarily by reducing respiratory rate. This results from direct effects on the preBötzinger Complex as well as from depression of the Parabrachial/Kölliker-Fuse Complex, which provides excitatory drive to preBötzinger Complex neurons mediating respiratory phase-switch. Opioids also depress awake drive from the forebrain and chemodrive.

The Pharmacodynamic Effect of a Remifentanil Bolus on Ventilatory Control

2000 ◽  
Vol 92 (2) ◽  
pp. 393-393 ◽  
Author(s):  
H. Daniel Babenco ◽  
Pattilyn F. Conard ◽  
Jeffrey B. Gross
Keyword(s):  
Carbon Dioxide ◽  
Respiratory Depression ◽  
Response Curve ◽  
Time Course ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Effect Site ◽  
Ventilatory Drive ◽  
Ventilatory Depression ◽  
Carbon Dioxide Response

Background In doses typically administered during conscious sedation, remifentanil may be associated with ventilatory depression. However, the time course of ventilatory depression after an initial dose of remifentanil has not been determined previously. Methods In eight healthy volunteers, the authors determined the time course of the ventilatory response to carbon dioxide using the dual isohypercapnic technique. Subjects breathed via mask from a to-and-fro circuit with variable carbon dioxide absorption, allowing the authors to maintain end-tidal pressure of carbon dioxide (PET(CO2)) at approximately 46 or 56 mm Hg (alternate subjects). After 6 min of equilibration, subjects received 0.5 microg/kg remifentanil over 5 s, and minute ventilation (V(E)) was recorded during the next 20 min. Two hours later, the study was repeated using the other carbon dioxide tension (56 or 46 mm Hg). The V(E) data were used to construct two-point carbon dioxide response curves at 30-s intervals after remifentanil administration. Using published pharmacokinetic values for remifentanil and the method of collapsing hysteresis loops, the authors estimated the effect-site equilibration rate constant (k(eo)), the effect-site concentration producing 50% respiratory depression (EC50), and the shape parameter of the concentration-response curve (gamma). Results The slope of the carbon dioxide response decreased from 0.99 [95% confidence limits 0.72 to 1.26] to a nadir of 0.27 l x min(-1) x mm Hg(-1) [-0.12 to 0.66] 2 min after remifentanil (P<0.001); within 5 min, it recovered to approximately 0.6 l x min(-1) x mm Hg(-1), and within 15 min of injection, slope returned to baseline. The computed ventilation at PET = 50 mm Hg (VE50) decreased from 12.9 [9.8 to 15.9] to 6.1 l/min [4.8 to 7.4] 2.5 min after remifentanil injection (P<0.001). This was caused primarily by a decrease in tidal volume rather than in respiratory rate. Estimated pharmacodynamic parameters based on computed mean values of VE50 included k(eo) = 0.24 min(-1) (T1/2 = 2.9 min), EC50 = 1.12 ng/ml, and gamma = 1.74. Conclusions After administration of 0.5 microg/kg remifentanil, there was a decrease in slope and downward shift of the carbon dioxide ventilatory response curve. This reached its nadir approximately 2.5 min after injection, consistent with the computed onset half-time of 2.9 min. The onset of respiratory depression appears to be somewhat slower than previously reported for the onset of remifentanil-induced electroencephalographic slowing. Recovery of ventilatory drive after a small dose essentially was complete within 15 min.

Ventilatory Response to Hypercapnia as Experimental Model to Study Effects of Oxycodone on Respiratory Depression

2021 ◽  
Vol 16 ◽  
Author(s):  
Lynn R. Webster ◽  
Erik Hansen ◽  
Gregory J. Stoddard ◽  
Austin Rynders ◽  
David Ostler ◽  
...  
Keyword(s):  
Respiratory Depression ◽  
Ventilatory Response ◽  
Volume Flow Rate ◽  
Minute Ventilation ◽  
Statistical Significance ◽  
Adult Males ◽  
Post Dose ◽  
Double Blind ◽  
End Tidal ◽  
End Tidal Co2

Background: Opioid analgesics used to treat pain can cause respiratory depression. However, this effect has not been extensively studied, and life- threatening, opioid-induced respiratory depression remains difficult to predict. We tested the ventilatory response to hypercapnia for evaluating the pharmacodynamic effect of a drug on respiratory depression. Methods: We conducted a randomized, placebo-controlled, double-blind, crossover, study in 12 healthy adult males. Subjects received 2 treatments (placebo and immediate-release oxycodone 30 mg) separated by a 24-hour washout period. Subjects inhaled a mixture of 7% carbon dioxide, 21% oxygen, and 72% nitrogen for 5 minutes to assess respiratory depression. Minute ventilation, respiratory rate, tidal volume, flow rate, end-tidal CO2, and oxygen saturation were recorded continuously at pre-dose and 30, 60, 120, and 180 minutes post-dose. The primary endpoint was the effect on ventilatory response to hypercapnia at 60 minutes post-dose, as assessed by the slope of the linear relationship between minute ventilation and end-tidal CO2. Results: At 60 minutes post-dose, subjects had a mean slope of 2.4 in the oxycodone crossover period, compared to 0.1 in the placebo period (mean difference, 2.3; 95%CI: 0.2 to 4.5; p = 0.035). Statistical significance was likewise achieved at the secondary time points (30, 120, and 180 minutes post-dose, p <0.05). Conclusions: This model for testing ventilatory response to hypercapnia discriminated the effect of 30 mg of oxycodone vs. placebo for up to 3 hours after a single dose. It may serve as a method to predict the relative effect of a drug on respiratory depression.

5-HT1A Receptor Agonist Befiradol Reduces Fentanyl-induced Respiratory Depression, Analgesia, and Sedation in Rats

2015 ◽  
Vol 122 (2) ◽  
pp. 424-434 ◽  
Author(s):  
Jun Ren ◽  
Xiuqing Ding ◽  
John J. Greer
Keyword(s):  
Respiratory Depression ◽  
Receptor Agonist ◽  
Minute Ventilation ◽  
Pharmacological Therapy ◽  
Behavioral Syndrome ◽  
Adult Rats ◽  
Righting Reflex ◽  
And Behavior ◽  
Neural Discharge

Abstract Background: There is an unmet clinical need to develop a pharmacological therapy to counter opioid-induced respiratory depression without interfering with analgesia or behavior. Several studies have demonstrated that 5-HT1A receptor agonists alleviate opioid-induced respiratory depression in rodent models. However, there are conflicting reports regarding their effects on analgesia due in part to varied agonist receptor selectivity and presence of anesthesia. Therefore the authors performed a study in rats with befiradol (F13640 and NLX-112), a highly selective 5-HT1A receptor agonist without anesthesia. Methods: Respiratory neural discharge was measured using in vitro preparations. Plethysmographic recording, nociception testing, and righting reflex were used to examine respiratory ventilation, analgesia, and sedation, respectively. Results: Befiradol (0.2 mg/kg, n = 6) reduced fentanyl-induced respiratory depression (53.7 ± 5.7% of control minute ventilation 4 min after befiradol vs. saline 18.7 ± 2.2% of control, n = 9; P &lt; 0.001), duration of analgesia (90.4 ± 11.6 min vs. saline 130.5 ± 7.8 min; P = 0.011), duration of sedation (39.8 ± 4 min vs. saline 58 ± 4.4 min; P = 0.013); and induced baseline hyperventilation, hyperalgesia, and “behavioral syndrome” in nonsedated rats. Further, the befiradol-induced alleviation of opioid-induced respiratory depression involves sites or mechanisms not functioning in vitro brainstem–spinal cord and medullary slice preparations. Conclusions: The reversal of opioid-induced respiratory depression and sedation by befiradol in adult rats was robust, whereas involved mechanisms are unclear. However, there were adverse concomitant decreases in fentanyl-induced analgesia and altered baseline ventilation, nociception, and behavior.

Respiratory nuclei share synaptic connectivity with pontine reticular regions regulating REM sleep

1995 ◽  
Vol 268 (2) ◽  
pp. L251-L262 ◽  
Author(s):  
L. H. Lee ◽  
D. B. Friedman ◽  
R. Lydic
Keyword(s):  
Respiratory Depression ◽  
Rem Sleep ◽  
Minute Ventilation ◽  
Fluorescent Labeling ◽  
Respiratory Neurons ◽  
Synaptic Connectivity ◽  
Fluorescent Tracers ◽  
State Dependent ◽  
Dorsal Respiratory Group ◽  
Diamidino Yellow

Injection of cholinomimetics into the medial pontine reticular formation (mPRF) of intact, unanesthetized cat causes a rapid eye movement (REM) sleep-like state and respiratory depression. The mPRF contains no concentrations of respiratory neurons, and this study examined the hypothesis that respiratory depression evoked from the mPRF is synaptically mediated. The mPRF of conscious cats was injected with bethanechol to define an mPRF zone causing state-dependent respiratory depression. Bethanechol caused a 361% increase in the REM sleep-like state and a 37% decrease in minute ventilation. Additional cats were injected with the retrograde fluorescent tracers True Blue and either Fluoro-Gold or Diamidino Yellow aimed for the cholinoceptive mPRF or for the pontine respiratory group (PRG). After mPRF dye injection, 1) labeling was observed in the PRG, dorsal respiratory group (DRG), and ventral respiratory group (VRG); and 2) double-labeled cells were observed in the VRG and PRG. Dye injections into the PRG produced contralateral and ipsilateral fluorescent labeling of the mPRF, DRG, and VRG. Thus cholinoceptive regions of the mPRF involved in REM sleep generation have reciprocal monosynaptic connections with the PRG and receive monosynaptic projections from the DRG and VRG.

Dexmedetomidine Pharmacodynamics: Part I

2004 ◽  
Vol 101 (5) ◽  
pp. 1066-1076 ◽  
Author(s):  
Yung-Wei Hsu ◽  
Luis I. Cortinez ◽  
Kerri M. Robertson ◽  
John C. Keifer ◽  
Sam T. Sum-Ping ◽  
...  
Keyword(s):  
Respiratory Rate ◽  
Respiratory Depression ◽  
Cycle Time ◽  
Minute Ventilation ◽  
Respiratory Acidosis ◽  
Apnea Hypopnea Index ◽  
Sudden Increase ◽  
Inspiratory Time ◽  
Natural Sleep ◽  
Target Controlled Infusion

Background Dexmedetomidine, a highly selective alpha2-adrenoceptor agonist used for short-term sedation of mechanically ventilated patients, has minimal effect on ventilation. Methods This study compared the respiratory effect of dexmedetomidine to that of remifentanil. The authors measured and compared respiratory responses of six healthy male volunteers during (1) a stepwise target-controlled infusion of remifentanil, (2) a stepwise target-controlled infusion of dexmedetomidine, and (3) a pseudonatural sleep session. Results Compared with baseline, remifentanil infusions resulted in respiratory depression as evidenced by a decrease in respiratory rate and minute ventilation, respiratory acidosis, and apnea episodes resulting in desaturations. Remifentanil disturbed the natural pattern of breathing and flattened the distribution of ventilatory timing (inspiratory time/ventilatory cycle time). The respiratory effects of dexmedetomidine markedly contrasted with those of remifentanil. When compared with baseline, during dexmedetomidine infusions, the respiratory rate significantly increased, and the overall apnea/hypopnea index significantly decreased. The distribution of inspiratory time/ventilatory cycle time showed an increased peak. In addition, dexmedetomidine seemed to mimic some aspect of natural sleep. While the subjects were breathing a 5% CO2 mixture, hypercapnic arousal phenomena (documented by the Bispectral Index, the electroencephalogram, and sudden increase in the minute ventilation) were observed during dexmedetomidine infusions. Similar phenomena during natural sleep have been reported in the literature. Conclusions In comparison with remifentanil, dexmedetomidine infusions (1) did not result in clinically significant respiratory depression, (2) decreased rather than increased the apnea/hypopnea index, and (3) exhibited some similarity with natural sleep.

scholarly journals An effective combination of anaesthetics for 6-h experimentation in the golden Syrian hamster

1989 ◽  
Vol 23 (2) ◽  
pp. 156-162 ◽  
Author(s):  
W. D. Reid ◽  
C. Davies ◽  
P. D. Pare ◽  
R. L. Pardy
Keyword(s):  
Respiratory Depression ◽  
Minute Ventilation ◽  
Sodium Pentobarbital ◽  
Depth Of Anaesthesia ◽  
Golden Syrian Hamster ◽  
Arterial Blood ◽  
Effective Combination ◽  
Suitable Combination ◽  
Early Surgical Intervention

The anaesthetics described for use in hamsters to date are suitable for the performance of short-term experimentation. However, an anaesthetic regimen was required which would provide a stable preparation for 6 h and hence, a suitable combination was developed. In the first set of experiments, the effect of anaesthetics (chloralose, urethane, and pentobarbital) were examined alone and in combination on arterial blood measurements. In the second set of experiments the effect of the combination of anaesthetics on arterial blood measurements and minute ventilation was examined for up to 6 h. Chloralose, urethane and pentobarbital when used alone in the hamster were considered inadequate for our needs. Chloralose did not produce adequate surgical anaesthesia whereas urethane and pentobarbital resulted in marked respiratory depression. Urethane also produced a trend towards metabolic acidosis. In contrast, the combination of agents resulted in surgical anaesthesia and the arterial blood measurements were adequate. Further, the use of the combination of anaesthetics in hamsters resulted in a stable preparation where arterial blood measurements and minute ventilation were maintained in a good range for up to 6 h. The combination of chloralose, urethane and sodium pentobarbital in hamsters should prove useful in long-term non-recovery experimentation which requires early surgical intervention, minimal respiratory depression and an even depth of anaesthesia.

Effect of Flumazenil on Ventilatory Drive during Sedation with Midazolam and Alfentanil

1996 ◽  
Vol 85 (4) ◽  
pp. 713-720 ◽  
Author(s):  
Jeffrey B. Gross ◽  
Robert T. Blouin ◽  
Shaul Zandsberg ◽  
Pattilyn F. Conard ◽  
Jurgen Haussler
Keyword(s):  
Carbon Dioxide ◽  
Respiratory Depression ◽  
Minute Ventilation ◽  
Study Drug ◽  
Double Blind ◽  
Ventilatory Responses ◽  
Ventilatory Drive ◽  
To Receive ◽  
Blind Crossover Study ◽  
Double Blind Crossover Study

Background Patients who receive a combination of a benzodiazepine and an opioid for conscious sedation are at risk for developing respiratory depression. While flumazenil effectively antagonizes the respiratory depression associated with a benzodiazepine alone, its efficacy in the presence of both a benzodiazepine and an opioid has not been established. This study was designed to determine whether flumazenil can reverse benzodiazepine-induced depression of ventilatory drive in the presence of an opioid. Methods Twelve healthy volunteers completed this randomized, double-blind, crossover study. Ventilatory responses to carbon dioxide and to isocapnic hypoxia were determined during four treatment phases: (1) baseline, (2) alfentanil infusion; (3) combined midazolam and alfentanil infusions, and (4) combined alfentanil, midazolam, and "study drug" (consisting of either flumazenil or flumazenil vehicle) infusions. Subjects returned 2-6 weeks later to receive the alternate study drug. Results Alfentanil decreased the slope of the carbon dioxide response curve from 2.14 +/- 0.40 to 1.43 +/- 0.19 l.min-1.mmHg-1 (x +/- SE, P &lt; 0.05), and decreased the minute ventilation at P(ET)CO2 = 50 mmHg (VE50) from 19.7 +/- 1.2 to 14.8 +/- 0.9l.min-1 (P &lt; 0.05). Midazolam further reduced these variables to 0.87 +/- 0.17 l.min-1.mmHg-1 (P &lt; 0.05) and 11.7 +/- 0.8 l.min-1 (P &lt; 0.05), respectively. With addition of flumazenil, slope and VE50 increased to 1.47 +/- 0.37 l.min-1.mmHg-1 (P &lt; 0.05) and 16.4 +/- 2.0l.min-1 (P &lt; 0.05); after placebo, the respective values of 1.02 +/- 0.19 l.min-1.mmHg-1 and 12.5 +/- 1.2 l.min-1 did not differe significantly from their values during combined alfentanil and midazolam administration. The effect of flumazenil differed significantly from that of placebo (P &lt; 0.05). Both the slope and the displacement of the hypoxic ventilatory response, measured at P(ET)CO2 = 46 +/- 1 mmHG, were affected similarly, with flumazenil showing a significant improvement compared to placebo. Conclusions Flumazenil effectively reverses the benzodiazepine component of ventilatory depression during combined administration of a benzodiazepine and an opioid.

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