scholarly journals Modeling the Non–Steady State Respiratory Effects of Remifentanil in Awake and Propofol-sedated Healthy Volunteers

2010 ◽  
Vol 112 (6) ◽  
pp. 1382-1395 ◽  
Author(s):  
Erik Olofsen ◽  
Merel Boom ◽  
Diederik Nieuwenhuijs ◽  
Elise Sarton ◽  
Luc Teppema ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Steady State ◽  
Partial Pressure ◽  
Healthy Volunteers ◽  
Respiratory Depression ◽  
Low Dose ◽  
Carbon Dioxide Concentration ◽  
Model Parameters ◽  
State Models ◽  
End Tidal

Background Few studies address the dynamic effect of opioids on respiration. Models with intact feedback control of carbon dioxide on ventilation (non-steady-state models) that correctly incorporate the complex interaction among drug concentration, end-tidal partial pressure of carbon dioxide concentration, and ventilation yield reliable descriptions and predictions of the behavior of opioids. The authors measured the effect of remifentanil on respiration and developed a model of remifentanil-induced respiratory depression. Methods Ten male healthy volunteers received remifentanil infusions with different infusion speeds (target concentrations: 4-9 ng/ml; at infusion rates: 0.17-9 ng x ml x min) while awake and at the background of low-dose propofol. The data were analyzed with a nonlinear model consisting of two additive linear parts, one describing the depressant effect of remifentanil and the other describing the stimulatory effect of carbon dioxide on ventilation. Results The model adequately described the data including the occurrence of apnea. Most important model parameters were as follows: C50 for respiratory depression 1.6 +/- 0.03 ng/ml, gain of the respiratory controller (G) 0.42 - 0.1 l x min x Torr, and remifentanil blood effect site equilibration half-life (t(1/2)ke0) 0.53 +/- 0.2 min. Propofol caused a 20-50% reduction of C50 and G but had no effect on t(1/2)ke0. Apnea occurred during propofol infusion only. A simulation study revealed an increase in apnea duration at infusion speeds of 2.5-0.5 ng x ml x min followed by a reduction. At an infusion speed of < or = 0.31 ng x ml x min, no apnea was seen. Conclusions The effect of varying remifentanil infusions with and without a background of low-dose propofol on ventilation and end-tidal partial pressure of carbon dioxide concentration was described successfully using a non-steady-state model of the ventilatory control system. The model allows meaningful simulations and predictions.

Effect of intravenous dopamine on hypercapnic ventilatory response in humans

1983 ◽  
Vol 55 (5) ◽  
pp. 1418-1425 ◽  
Author(s):  
D. S. Ward ◽  
J. W. Bellville
Keyword(s):  
Carbon Dioxide ◽  
Ventilatory Response ◽  
Carbon Dioxide Concentration ◽  
Carbon Dioxide Tension ◽  
Model Parameters ◽  
Loop Gain ◽  
Loop Contribution ◽  
Dopamine Infusion ◽  
Hypercapnic Ventilatory Response ◽  
End Tidal

This study assessed the effect of low-dose intravenous dopamine (3 micrograms X kg-1 X min-1) on the hypercapnic ventilatory response in humans. Six normal healthy subjects were studied. By manipulating the inspired carbon dioxide concentration, the end-tidal carbon dioxide tension was raised in a stepwise fashion from 41 to 49 Torr and held at this level for 4 min. The end-tidal CO2 tension was then lowered back to 41 Torr in a stepwise fashion. The end-tidal O2 tension was held constant at 106 Torr throughout the experiment. The ventilatory response to this normoxic hypercapnic stimulus was analyzed by fitting two exponential functions, allowing the response to be separated into slow and fast chemoreflex loops. Each loop is described by a gain, time constant, and time delay. A single eupneic threshold was used for both loops. Nine control experiments and eight experiments performed during dopamine infusion were analyzed. The dopamine infusion caused the fast loop gain to be significantly (P less than 0.05) reduced from 0.64 to 0.19 l X min-1 X Torr-1, while the slow loop gain was unchanged. The fast loop contribution was reduced from 28 to 11% of the total ventilatory response. None of the other model parameters were significantly affected by the dopamine infusion. Exogenously administered dopamine substantially reduces the sensitivity of the fast chemoreflex loop to carbon dioxide.

scholarly journals Ventilatory parameters measured during a physiological study of simulated powered air-purifying respirator failure in healthy volunteers

2021 ◽  
pp. 0310057X2097898
Author(s):  
Lachlan F Miles ◽  
Timothy Makar ◽  
Chad W Oughton ◽  
Philip J Peyton
Keyword(s):  
Carbon Dioxide ◽  
Partial Pressure ◽  
Healthy Volunteers ◽  
Minute Ventilation ◽  
Peripheral Oxygen Saturation ◽  
Thermal Discomfort ◽  
Fraction Of Inspired Oxygen ◽  
Mechanical Devices ◽  
End Tidal ◽  
High Level

Powered air-purifying respirators (PAPR) are a high level of respiratory personal protective equipment. Like all mechanical devices, they are vulnerable to failure. The precise physiological consequences of failure in live subjects have not previously been reported. We conducted an observational safety study simulating PAPR failure in a group of nine healthy volunteers, wearing loose-fitting hoods, who were observed for a period of ten minutes, or until they requested the experiment be aborted, with continuous monitoring of gas exchange. Relative to baseline, participants demonstrated median reductions in peripheral oxygen saturation of 3.5% (95% confidence interval (CI) –4% to –2%; P = 0.0039) and fraction of inspired oxygen of 0.045 (95% CI –0.05 to –0.04; P = 0.0039), and median increases in inspired partial pressure of carbon dioxide of 27 mmHg (95% CI 23.5–32 mmHg; P = 0.0039), end-tidal partial pressure of carbon dioxide of 11 mmHg (95% CI 7–16 mmHg; P = 0.0039) and minute ventilation of 30 l/min (95% CI 19.4–35.9 l/min; P = 0.0039). Median collateral entrainment of room air into the hood was 17.6 l/min (interquartile range 12.3–27.0 l/min). All subjects reported thermal discomfort, with two (22.2%) requesting early termination of the experiment. Whilst the degree of rebreathing in this experiment was not sufficient to cause dangerous physiological derangement, the degree of reported thermal discomfort combined with the consequences of entrainment of possibly contaminated air into the hood, pose a risk to wearers in the event of failure.

scholarly journals Differential Effect of Morphine and Morphine-6-glucuronide on the Control of Breathing in the Anesthetized Cat

2008 ◽  
Vol 109 (4) ◽  
pp. 689-697 ◽  
Author(s):  
Luc J. Teppema ◽  
Eveline van Dorp ◽  
Babak Mousavi Gourabi ◽  
Jack W. van Kleef ◽  
Albert Dahan
Keyword(s):  
Carbon Dioxide ◽  
Respiratory Depression ◽  
Carbon Dioxide Concentration ◽  
Compartment Model ◽  
Central Component ◽  
Depressant Effect ◽  
End Tidal Carbon Dioxide ◽  
Mu Opioids ◽  
End Tidal ◽  
Anesthetized Cat

Background Morphine's metabolite, morphine-6-glucuronide (M6G), activates the mu-opioid receptor. Previous data suggest that M6G activates a unique M6G receptor that is selectively antagonized by 3-methoxynaltrexome (3mNTX). The authors compared the effects of M6G and morphine on breathing in the anesthetized cat and assessed whether 3mNTX reversal was selective for M6G. Methods Step changes in end-tidal carbon dioxide concentration were applied in cats anesthetized with alpha-chloralose-urethane. In study 1, the effect of the 0.15 mg/kg morphine followed by 0.2 mg/kg 3mNTX and next 0.8 mg/kg M6G was assessed in six cats. In study 2, the effect of 0.8 mg/kg M6G followed by 0.2 mg/kg 3mNTX and 0.15 mg/kg morphine was tested in another six cats. The ventilatory carbon dioxide responses were analyzed with a two-compartment model of the ventilatory controller, which consists of a fast peripheral and a slow central component. Results Both opioids shifted the ventilatory carbon dioxide responses to higher end-tidal carbon dioxide levels. Morphine had a preferential depressant effect within the central chemoreflex loop. In contrast, M6G had a preferential depressant effect within the peripheral chemoreflex loop. Irrespective of the opioid, 3mNTX caused full reversal of and prevented respiratory depression. Conclusions In anesthetized cats, the mu-opioids morphine and M6G induce respiratory depression at different sites within the ventilatory control system. Because 3mNTX caused full reversal of the respiratory depressant effects of both opioids, it is unlikely that a 3mNTX-sensitive unique M6G receptor is the cause of the differential respiratory behavior of morphine and M6G.

Ventilatory Response to Hypoxia in Humans

1996 ◽  
Vol 85 (1) ◽  
pp. 60-68 ◽  
Author(s):  
Albert Dahan ◽  
Elise Sarton ◽  
Maarten van den Elsen ◽  
Jack van Kleef ◽  
Luc Teppema ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Partial Pressure ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Carbon Dioxide Concentration ◽  
Detectable Effect ◽  
Hypoxic Ventilatory Response ◽  
Anesthetic Agents ◽  
Carotid Bodies ◽  
End Tidal

Background At low dose, the halogenated anesthetic agents halothane, isoflurane, and enflurane depress the ventilatory response to isocapnic hypoxia in humans. In the current study, the influence of subanesthetic desflurane (0.1 minimum alveolar concentration [MAC]) on the isocapnic hypoxic ventilatory response was assessed in healthy volunteers during normocapnia and hypercapnia. Methods A single hypoxic ventilatory response was obtained at each of 4 target end-tidal partial pressure of oxygen concentrations: 75, 53, 44, and 38 mmHg, before and during 0.1 MAC desflurane administration. Fourteen subjects were tested at a normal end-tidal partial pressure of carbon dioxide (43 mmHg), with 9 subjects tested at an end-tidal carbon dioxide concentration of 49 mmHg (hypercapnia). The hypoxic sensitivity (S) was computed as the slope of the linear regression of inspired minute ventilation (V1) on (100-SPO2). Values are mean +/- SE. Results Sensitivity was unaffected by desflurane during normocapnia (control: S = 0.45 +/- 0.07 l.min-1.%-1 vs. 0.1 MAC desflurane: S = 0.43 +/- 0.09 l.min-1.%-1). With hypercapnia S decreased by 30% during desflurane inhalation (control: S = 0.74 +/- 0.09 l.min-1.%-1 vs. 0.1 MAC desflurane: S = 0.53 +/- 0.06 l.min-1.%-1; P < 0.05). Conclusions On the basis of the data, subanesthetic desflurane has no detectable effect on the normocapnic hypoxic ventilatory response sensitivity. However, the carbon dioxideinduced augmentation of the hypoxic response was reduced. This indicates that subanesthetic desflurane effects the chemoreceptors at the carotid bodies.

Cerebrovascular time constant: dependence on cerebral perfusion pressure and end-tidal carbon dioxide concentration

2012 ◽  
Vol 34 (1) ◽  
pp. 17-24 ◽  
Author(s):  
Marek Czosnyka ◽  
Hugh K Richards ◽  
Matthias Reinhard2 ◽  
Luzius A Steiner3 ◽  
Karol Budohoski ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Cerebral Perfusion Pressure ◽  
Time Constant ◽  
Cerebral Perfusion ◽  
Perfusion Pressure ◽  
Carbon Dioxide Concentration ◽  
End Tidal Carbon Dioxide ◽  
End Tidal

Effects of step changes in pH on isometric tetanic tension of toad sartorius muscle

1983 ◽  
Vol 61 (8) ◽  
pp. 830-835 ◽  
Author(s):  
J. M. Renaud ◽  
E. Don Stevens
Keyword(s):  
Carbon Dioxide ◽  
Steady State ◽  
Rapid Change ◽  
Carbon Dioxide Concentration ◽  
Physiological Solution ◽  
Acclimation Temperature ◽  
Sartorius Muscle ◽  
Bathing Solution ◽  
Ph Change ◽  
Tetanic Tension

The effect of a rapid change in pHe (pH of bathing solution) on the isometric tetanic tension developed by sartorius muscles of toads acclimated to 5 and 25 °C was measured at 5 and 25 °C. The pH was altered by changing the carbon dioxide concentration of a bicarbonate buffered physiological solution. Acclimation temperature did not modify the response to a rapid change in pH, but test temperature did. Following a pH decrease from 9.0 to 6.0, tetanic tension decreased at a faster rate at 5 °C than at 25 °C. A new steady state was reached in 15 min at 5 °C but in 40 min at 25 °C. Following a pH increase from 6.0 to 8.5, tetanic tension increased at a faster rate at 25 °C than at 5 °C. A new steady state was reached in 60 min at 5 °C but in 10 min at 25 °C. We conclude that the rate of carbon dioxide diffusion through the sartorius muscle is only one factor that determines how rapidly tetanic tension changes following the step change in pH, and that muscle resists pH change more effectively at higher temperatures.

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