Influence of haemorrhage on the pseudo-steady-state remifentanil concentration in a swine model: a comparison with propofol and the effect of haemorrhagic shock stage

Kurita, Tadayoshi; Uraoka, Masahiro; Morita, Koji; Suzuki, Minoru; Morishima, Yoriko; Sato, Shigehito

doi:10.1093/bja/aer233

Cited by 13 publications

(8 citation statements)

References 17 publications

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“…It is in agreement with our study, as the model predicted CO is a better surrogate of liver blood flow than measured CO. Similarly, the animal studies confirm the significance of CO in predicting propofol concentrations during constant infusion [48][49][50]. In all these studies the plasma remifentanil and propofol concentrations were influenced by CO during continuous infusions, with concentrations decreasing with increased CO and increasing with decreased CO.…”

Section: Model Simulations and Clinical Significancesupporting

confidence: 64%

“…In all these studies the plasma remifentanil and propofol concentrations were influenced by CO during continuous infusions, with concentrations decreasing with increased CO and increasing with decreased CO. In our study CO changes occurred as a result of inter-and intra-patient variability connected with patients' individual characteristics and clinical scenario, whereas in the animal studies by Kurita et al [48][49][50], the animals were divided into groups based on the CO maintained throughout the study. Also, it is consistent with the physiologically-based models of propofol or fentanyl [13,51] which show CO as a main determinant of drug clearances.…”

Section: Model Simulations and Clinical Significancementioning

confidence: 94%

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The influence of cardiac output on propofol and fentanyl pharmacokinetics and pharmacodynamics in patients undergoing abdominal aortic surgery

Bienert

Sobczyński

Młodawska

et al. 2020

J Pharmacokinet Pharmacodyn

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Cardiac output (CO) is expected to affect elimination and distribution of highly extracted and perfusion rate-limited drugs. This work was undertaken to quantify the effect of CO measured by the pulse pressure method on pharmacokinetics and pharmacodynamics of propofol and fentanyl administrated during total intravenous anesthesia (TIVA). The data were obtained from 22 ASA III patients undergoing abdominal aortic surgery. Propofol was administered via target-controlled infusion system (Diprifusor) and fentanyl was administered at a dose of 2-3 lg/kg each time analgesia appeared to be inadequate. Hemodynamic measurements as well as bispectral index were monitored and recorded throughout the surgery. Data analysis was performed by using a non-linear mixed-effect population modeling (NONMEM 7.4 software). Three compartment models that incorporated blood flows as parameters were used to describe propofol and fentanyl pharmacokinetics. The delay of the anesthetic effect, with respect to plasma concentrations, was described using a biophase (effect) compartment. The bispectral index was linked to the propofol and fentanyl effect site concentrations through a synergistic E max model. An empirical linear model was used to describe CO changes observed during the surgery. Cardiac output was identified as an important predictor of propofol and fentanyl pharmacokinetics. Consequently, it affected the depth of anesthesia and the recovery time after propofol-fentanyl TIVA infusion cessation. The model predicted (not observed) CO values correlated best with measured responses. Patients' age was identified as a covariate affecting the rate of CO changes during the anesthesia leading to age-related difference in individual patient's responses to both drugs.

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Section: Model Simulations and Clinical Significancesupporting

confidence: 64%

Section: Model Simulations and Clinical Significancementioning

confidence: 94%

The influence of cardiac output on propofol and fentanyl pharmacokinetics and pharmacodynamics in patients undergoing abdominal aortic surgery

Bienert

Sobczyński

Młodawska

et al. 2020

J Pharmacokinet Pharmacodyn

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“…The median (range) summarized anesthetic depth score was 4 (3)(4)(5) in both groups, while the median (range) BSR was 3 (0-27) in the propofol group, and 2 (1-53) in the alfaxalone group. EEG was evaluated in the last seven pigs of the experiment.…”

Section: Resultsmentioning

confidence: 92%

Macrocirculatory Parameters and Oxygen Debt Indices in Pigs During Propofol Or Alfaxalone Anesthesia When Subjected to Experimental Stepwise Hemorrhage

et al. 2021

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Background: Pigs are anesthetized when used for emergency procedures live tissue training (LTT) of civilian and military medical personnel or for experimental purposes, but there is a paucity in the literature regarding anesthesia of pigs for this purpose.Objective(s): The main goals of the study were to compare oxygen debt, macrocirculatory parameters, and time to cardiac arrest between pigs in hemorrhagic shock and anesthetized with propofol-ketamine-dexmedetomidine or alfaxalone-ketamine-dexmedetomidine.Design: A prospective, non-blinded randomized study design was used. Sixteen pigs were randomized in blocks of four to be anesthetized with either propofol-ketamine-dexmedetomidine (n = 8) or alfaxalone-ketamine-dexmedetomidine (n = 8) as a continuous infusion.Interventions: Premedication with ketamine 15 mg kg−1 and midazolam 1 mg kg−1 was given i.m. Anesthesia was maintained with propofol 8 mg kg−1 h−1 or alfaxalone 5 mg kg−1 h−1 combined with ketamine 5 mg kg−1 h−1 and dexmedetomidine 4 μg kg−1 h−1 i.v. A stepwise, volume-controlled model for hemorrhage was created by exsanguination.Main Outcome Measures: Indices of oxygen debt (lactate, base excess, and oxygen extraction), macrocirculatory (PR, SAP, DAP, MAP, and CI, SVI, and TPR) variables, and time to death was compared between groups.Results: Pigs in the alfaxalone group had significantly higher SAP than pigs given propofol. No difference in other macrocirculatory variables or indices of oxygen debt could be found. A blood loss of 50% of the total blood volume or more was possible in most pigs with both anesthetic regimes.Conclusions: Pigs anesthetized with propofol or alfaxalone combined with ketamine and dexmedetomidine tolerated substantial blood loss.

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“…5 (28) No resuscitation 100% 4Y5.5 h Investigation of the influence of hemorrhage on the pseudoYsteady-state remifentanil concentration compared with the changes with those for propofol (30) Group 1: 400 mg/kg valproic acid (VPA) in a volume of 1.33 mL/kg over 2 min 100% 6 h Effects of VPA and pentoxifylline (PTX) on resuscitation after hemorrhagic shock in pigs (12) (Continued on next page) (16,17). 5 (28) No resuscitation 100% 4Y5.5 h Investigation of the influence of hemorrhage on the pseudoYsteady-state remifentanil concentration compared with the changes with those for propofol (30) Group 1: 400 mg/kg valproic acid (VPA) in a volume of 1.33 mL/kg over 2 min 100% 6 h Effects of VPA and pentoxifylline (PTX) on resuscitation after hemorrhagic shock in pigs (12) (Continued on next page) (16,17).…”

Section: In Vivo Models For Mimicking the Clinical Entitymentioning

confidence: 99%

“…The advantage of a volume-controlled model is the ability to assess compensatory hemodynamic mechanisms. However, depending on the study design as lethal models, mortality rates of up to 100% have been described (10,12,29,30). In most studies, a 30% to 50% reduction in total blood volume has been induced, resulting in mortality rates up to 20% (22, 25Y28).…”

Section: Differences In Models Of Volume Controlled Vs Pressure Contmentioning

confidence: 99%

Combined Hemorrhage/Trauma Models in Pigs—Current State and Future Perspectives

Hildebrand¹,

Andruszkow

Huber‐Lang

et al. 2013

Shock

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The majority of injury combinations in multiply injured patients entail the chest, abdomen, and extremities. Numerous pig models focus on the investigation of posttraumatic pathophysiology, organ performance monitoring and on potential treatment options. Depending on the experimental question, previous authors have included isolated insults (controlled or uncontrolled hemorrhage, chest trauma) or a combination of these injuries (hemorrhage with abdominal trauma, chest trauma, traumatic brain injury, and/or long-bone fractures). Combined trauma models in pigs can provide a high level of clinical relevance, when they are properly designed and mimicking the clinical situation. Most of these models focus on the first hours after trauma, to assess the acute sequel of traumatic hemorrhage. However, hemorrhagic shock and the associated mass transfusion are also major causes for organ failure and mortality in the later clinical course. Thus, most models lack information on the pathomechanisms during the late posttraumatic phase. Studying new therapies only during the early phase is also not reflective of the clinical situation. Therefore, a longer observation period is required to study the effects of therapeutic approaches during intensive care treatment when using animal models. These long-term studies of combined trauma models will allow the development of valuable therapeutic approaches relevant for the later posttraumatic course. This review summarizes the existing porcine models and outlines the need for long-term models to provide real effective novel therapeutics for multiply injured patients to improve organ function and clinical outcome.

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Influence of haemorrhage on the pseudo-steady-state remifentanil concentration in a swine model: a comparison with propofol and the effect of haemorrhagic shock stage

Abstract: During haemorrhage, the plasma remifentanil concentration showed a three-fold greater increase than that of propofol in administration by continuous infusion.

Cited by 13 publications

References 17 publications

The influence of cardiac output on propofol and fentanyl pharmacokinetics and pharmacodynamics in patients undergoing abdominal aortic surgery

The influence of cardiac output on propofol and fentanyl pharmacokinetics and pharmacodynamics in patients undergoing abdominal aortic surgery

Macrocirculatory Parameters and Oxygen Debt Indices in Pigs During Propofol Or Alfaxalone Anesthesia When Subjected to Experimental Stepwise Hemorrhage

Combined Hemorrhage/Trauma Models in Pigs—Current State and Future Perspectives

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