State of the art: Sedation concepts with volatile anesthetics in critically Ill patients

doi:10.1016/j.jcrc.2009.01.003

Journal of Critical Care

Volume 24, Issue 4, December 2009, Pages 535-544

https://doi.org/10.1016/j.jcrc.2009.01.003 Get rights and content

Abstract

The use of volatile anesthetics in the intensive care unit (ICU) has only been possible at great cost with the use of commercially available anesthesia systems. A new anesthetic-conserving device (AnaConDa^™) now facilitates, from a technical viewpoint, the routine use of volatile anesthetics in intensive care patients as part of prolonged sedation, using ICU ventilators. The volatile anesthetic is hereby applied continually via a syringe pump into a miniature vaporizer, which is integrated into the ventilator circuit in place of the usual respiratory filter. During expiration, the anesthetic exhaled by the patient enters the recirculation system, is predominantly stored in the active carbon layer of the anesthetic-conserving device, and redirected into the inspiratory air. At clinically relevant concentrations, more than 90% of the gas is recirculated in such a way. Aside from the possibility of using a central anesthetic gas scavenging system, the use of special passive residual gas filters, which can be connected to the expiratory outlet of the respirator machine, appears above all to be practical. The use of volatile anesthetics on the ICU could adopt a permanent position in various intensive care analgosedation concepts in future. It may be possible thereby to optimize the treatment process both in medical and economical terms.

Introduction

Still a few years ago, optimizing analgosedation has been neglected in intensive care research as well as in everyday clinical practice. Generally, hitherto deep sedation was the aim in intensive care patients. Today, more sophisticated sedation concepts have priority. The objectives of these concepts implies that the patient is free from pain and stress, and he or she is able to breathe spontaneously. Therefore, in daily practice, propofol is preferred for sedation up to 72 hours and midazolam for long-term sedation [1]. In addition, remifentanil is used increasingly as the basic substance of the analgesic-based sedation concept, which offers the most appropriate pharmacodynamic profile that allows a controllable sedation over the time [2]. Nevertheless, the daily practice of these concepts still reveals a variety of unsolved problems and drug-specific side effects. Propofol is limited for use up to 4 mg kg⁻¹ h⁻¹ up to 7 days because of the risk of the propofol infusion syndrome [3]. Furthermore, negative hemodynamic effects are observed, especially in cardiac insufficient and hypovolemic patients [4]. For benzodiazepines, an increased tolerance (“ceiling effect”), possible accumulation after long-term use, and an increased risk of an acute withdrawal syndrome are described [5]. Insufficient sedation quality as well as multiple sedation approaches (polypragmatism) in patients that are difficult to sedate result in a prolonged awakening and severe cognitive deficits after long-term use [5], [6]. Up to today, no ideal concept for analgosedation in intensive care patients exists.

Therefore sedation with volatile anesthetics in critical care patients (“inhalative sedation”) could be a useful supplement to present intravenous analgosedation protocols in the future. Knowing from general anesthesia, volatile sedatives are beneficial compared to total intravenous anesthetics regarding an optimized dose-response relationship facilitating an easy titration until a specific effect is achieved. Furthermore, protective effects on several organs and improved cognitive functions are described [7].

The following review describes the technical aspects of (long-term) inhalative sedation in critical care patients and discusses the current standards of knowledge in the use of volatile substances in intensive care.

Section snippets

Protective effects of volatile anesthetics

Volatile anesthetics have some cardioprotective and cerebroprotective properties. The term anesthetic preconditioning implies a protective effect from volatile anesthetics mediated by the opening of Adenosintriphosphate (ATP)-dependent potassium channels, which are also responsible for cardioprotection during ischemic preconditioning [8], [9]. Volatile anesthetics have on the one hand a negative inotropic effect, diminishing the left-ventricular afterload, and on the other hand a negative

Technical possibilities of inhalative sedation

There are reports of volatile anesthetics, particularly isoflurane, having been used successfully in intensive care since the end of the 1980s. Anesthetic gases were administered initially via the usual vaporizer in combination with a respirator (eg, Servo 900 C) and later as part of “closed anesthesia system” [13], [14]. With the development of an Anesthetic Conserving Device (AnaConDa^™, Sedana Medical, Uppsala, Sweden) in 1999 and the official presentation in the years 2004/2004, it is

Options for residual gas scavenging

When using volatile anesthetics, the potential health risks to staff exposed to such substances always have to be considered. Benchmarks for workplace exposure are determined by a regulation of the National Institute of Occupational Safety and Health [19]. In Europe, the latest amendment to the Hazardous Substances Ordinance in 2005 introduced a new concept of health-related limitations. The previously used term maximum allowable concentration (MAC) was replaced by occupational exposure limit

Inhalative sedation—clinical experience

Clinical studies and individual cases (Table 1, Table 2) have already been able to demonstrate that the use of isoflurane during intensive care in certain patient groups (eg, patients difficult to sedate, patients with bronchial asthma, epilepsy) offers clear benefits over intravenous analgosedation (eg, improved sedation quality, shorter recovery time). Korth et al [24], for example, evaluated 20 ventilated patients following sedation with isoflurane (2-27 days) and, apart from a clearly

Limitations

From a medical point of view, the question of the toxicity of the degradation products arises during long-term use (eg, fluoride). Studies have been able to demonstrate that there is in fact a transient increase in the measured fluoride concentration after just a short time, but this was of no clinical relevance even after prolonged application [38], [54]. Spencer et al [54] examined the fluoride concentrations during sedation with isoflurane for less than 24 hours and midazolam in a total of

Conclusion

So far, experience has shown that administration of the inhalational anesthetics isoflurane and sevoflurane in intensive care has been considerably simplified by the AnaConDa^™-system. The available methods for residual gas filtering appear to be efficient. The current issues of environmental protection are also taken into account by the possibility of residual gas recovery and potential recycling.

The implied simplicity of the system could also open up the hitherto specialized area of

References (54)

CremerO.L. et al.
Long-term propofol infusion and cardiac failure in adult head-injured patients
Lancet.
(2001)
KressJ.P. et al.
Delirium and sedation
Crit Care Clin
(2004)
EngelhardK. et al.
Desflurane and isoflurane improve neurologic outcome after incomplete cerebral ischemia in rats
Br J Anaesth
(1999)
KehlF. et al.
Sevoflurane-induced preconditioning of rat brain in vitro and the role of KATP channels
Brain Res
(2004)
MeiserA. et al.
Desflurane compared with propofol for postoperative sedation in the intensive care unit
Br J Anaesth
(2003)
PerhagL. et al.
The Reflector: a new method for saving anaesthetic vapours
Br J Anaesth
(2000)
MeiserA. et al.
Inhalational anaesthetics in the ICU: theory and practice of inhalational sedation in the ICU, economics, risk-benefit
Best Pract Res Clin Anaesthesiol
(2005)
JohnstonR.G. et al.
Isoflurane therapy for status asthmaticus in children and adults
Chest
(1990)
MartinJ. et al.
Practice of sedation and analgesia in German intensive care units: results of a national survey
Crit Care
(2005)
BreenD. et al.
Decreased duration of mechanical ventilation when comparing analgesia-based sedation using remifentanil with standard hypnotic-based sedation for up to 10 days in intensive care unit patients: a randomised trial
Crit Care
(2005)

BurnsA.M. et al.

The use of sedative agents in critically ill patients

Drugs

(1992)

ShaferA.

Complications of sedation with midazolam in the intensive care unit and a comparison with other sedative regimens

Crit Care Med

(1998)

GuptaA. et al.

Comparison of recovery profile after ambulatory anesthesia with propofol, isoflurane, sevoflurane and desflurane: a systematic review

Anesth Analg

(2004)

KehlF. et al.

Organprotektion durch volatile Anästhetika

Anästhesiologie und Intensivmedizin

(2004)

Tassani-PrellP. et al.

Einbau von Narkosegasvaporen in der Herz-Lungen- Maschine

Anästh Intensivmed

(2005)

WernerC. et al.

Sevoflurane improves neurological outcome after incomplete cerebral ischaemia in rats

Br J Anaessth

(1985)

LehmannG. et al.

Technische Vorraussetzungen für die Langzeitsedierung mit volatilen Anästhetika (Isofluran)

JungC. et al.

Use of sevoflurane sedation by the AnaConDa^™((R)) device as an adjunct to extubation in a pediatric burn patient

Burns

(2007)

SackeyP.V. et al.

Three cases of PICU sedation with isoflurane delivered by the ‘AnaConDa^™’

Paediatr Anaesth

(2005)

NIOSH

Criteria for a recommended standard: occupational exposure to anesthetic gases and vapors

(1977)

DGAI/BDA (Hrsg.): Umsetzung der Gefahrstoffverordnung Entschlieβungen-Empfehlungen-Vereinbarungen-Leitlinien: 365-372....

SackeyP.V. et al.

Ambient isoflurane pollution and isoflurane consumption during intensive care unit sedation with the Anesthetic Conserving Device

Crit Care Med

(2005)

Inghausen JG: Gutachten Sicherheit des NovaSorb-Filtersystem bei der Verwendung des Narkosegas-Rezirkulationssystems...

HoeraufK. et al.

Exposure of intensive care personnel to isoflurane in long-term sedation

Anasthesiol Intensivmed Notfallmed Schmerzther

(1995)

KorthM. et al.

Erste klinische Erfahrungen in der Langzeitsedierung mit Isofluran

StuttmannR. et al.

Sedierung mit Isofluran unter pulmonalen und hämodynamischen Aspekten

KongK.L. et al.

Isoflurane compared with midazolam for sedation in the intensive care unit

BMJ

(1989)

Cited by (81)

Guidelines for inhaled sedation in the ICU
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En las unidades de cuidados intensivos (UCI) la sedación se utiliza para mejorar el bienestar y la tolerancia durante la ventilación mecánica, en las intervenciones invasivas y durante los cuidados de enfermería. En los últimos años está aumentando el empleo de anestésicos inhalatorios con esta finalidad. Nuestro objetivo fue obtener y resumir la mejor evidencia existente en la sedación inhalada en pacientes adultos en la UCI. Y con ello asistir a los profesionales médicos en la selección de la estrategia más adecuada en este campo, abordando el impacto en los resultados y el riesgo/beneficio de su aplicación.
Debido a la insuficiente bibliografía y evidencia científica en varios aspectos del uso de la sedación inhalada en la UCI, entendimos justificado el empleo de una técnica Delphi para la creación de consensos. Se desarrolló siguiendo las recomendaciones de la guía CREDES, con una selección de 17 expertos y un periodo de trabajo de un año —entre 2022 y 2023—.
El trabajo realizado conllevó el desarrollo de la presente guía que incluye un total de 23 recomendaciones con consenso fuerte y 15 débiles.
El uso de la sedación inhalada en la UCI es una opción fiable y adecuada en una amplia variedad de escenarios clínicos. Aun así, creemos que existen numerosos aspectos que requieren ser estudiados en mayor profundidad.
Sedation is used in intensive care units (ICU) to improve comfort and tolerance during mechanical ventilation, invasive interventions, and nursing care. In recent years, the use of inhalation anaesthetics for this purpose has increased. Our objective was to obtain and summarize the best evidence on inhaled sedation in adult patients in the ICU, and use this to help physicians choose the most appropriate approach in terms of the impact of sedation on clinical outcomes and the risk-benefit of the chosen strategy.
Given the overall lack of literature and scientific evidence on various aspects of inhaled sedation in the ICU, we decided to use a Delphi method to achieve consensus among a group of 17 expert panellists. The processes was conducted over a 12-month period between 2022 and 2023, and followed the recommendations of the CREDES guidelines.
The results of the Delphi survey form the basis of these 39 recommendations - 23 with a strong consensus and 15 with a weak consensus.
The use of inhaled sedation in the ICU is a reliable and appropriate option in a wide variety of clinical scenarios. However, there are numerous aspects of the technique that require further study.
Inhaled sedation in the intensive care unit
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Citation Excerpt :
Importantly, halogenated agents undergo pulmonary elimination and have a low level of hepatic metabolism (metabolism rate of 2–5% for sevoflurane, 0.2% for isoflurane, and 0.02% for desflurane), without the production of active metabolites (fluorine ions) or alteration in hepatic/renal lab tests in patients [9]. Volatiles were first vaporised to ICU patients through anaesthesia machines to manage severe medical conditions, such as refractory asthma, bronchospasm and status epilepticus, or to achieve sedation in patients with high requirements, such as those with a history of drug abuse [7,19–23]. Nowadays, the anaesthetics machine has been repurposed to meet ICU demand in the current pandemic [24,25].
Inhaled sedation with halogenated agents, such as isoflurane or sevoflurane, is now feasible in intensive care unit (ICU) patients through dedicated vaporisers and scavenging systems. Such a sedation strategy requires specific equipment and adequate training of ICU teams. Isoflurane and sevoflurane have ideal pharmacological properties that allow efficient, well-tolerated, and titratable light-to-deep sedation. In addition to their function as sedative agents, these molecules may have clinical benefits that could be especially relevant to ICU patients. Our goal was to summarise the pharmacological basis and practical aspects of inhaled ICU sedation, review the available evidence supporting inhaled sedation as a viable alternative to intravenous sedation, and discuss the remaining areas of uncertainty and future perspectives of development.
Not a whiff: Sevoflurane for post-ROSC sedation on the ICU. Try it, you might like it
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This chapter reviews the critical care management of severe acute ischemic stroke and intracerebral hemorrhage. Some ischemic and hemorrhagic stroke patients have critical care needs, and recent evidence supports treatment in a specialized stroke unit or neurologic intensive care unit (ICU) to be associated with reduced mortality and a more favorable outcome as compared to general ICUs. Therapeutic approaches to even advanced or extensive acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) have increased considerably thereby altering the normal clinical course of previously devastating or otherwise fatal neurologic diagnoses. Numerous studies and guidelines have outlined airway management and ventilation, blood pressure management, the role of osmotherapy, targeted normothermia and hypothermia, and the use of advanced neuromonitoring in this clinical setting. Additionally, patients with AIS and ICH are at risk for secondary brain damage by various neurologic complications including increased intracranial pressure, reperfusion injury, perihematomal edema, and seizure as well as numerous systemic complications that often call for invasive or operative measures. Critical care expertise in the management of these complex patients is invaluable and depending on the collaboration of neurointensivists, vascular neurologists, neurosurgeons, specialized ICU nurses, and therapists. In summary, the initial management of complex AIS and ICH patients in many cases is best facilitated in focused neurologic ICUs with the collaboration of various medical practitioners. Ongoing studies continue to shed light on the most effective means to address primary neurologic injury and prevent secondary complications in these particular stroke patients threatened by death and disability.
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Minimal alveolar concentration for deep sedation (MAC-DS) in intensive care unit patients sedated with sevoflurane: A physiological study
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Citation Excerpt :
Indeed, volatile anaesthetic agents have favourable pharmacokinetics: pulmonary elimination, limited haepatic and renal metabolism, no accumulation, quick and consistent onset and offset of action [1,7]. Several trials support the efficacy and safety of volatile anaesthetic agents for the sedation in ICU patients [8,9]. Compared with intravenous agent, sevoflurane was associated with shorter wake-up and extubation times [10].
Volatile anaesthetic agents, especially sevoflurane, could be an alternative for sedating ICU patients. In the operating theatre, volatile anaesthetic agents are monitored using minimal alveolar concentration (MAC). In ICU, MAC may be used to assess sedation level and may replace clinical scale especially when they are unusable. Therefore, we sought to investigate the minimal sevoflurane end-tidal concentration to achieved deep sedation in critical ill patients: MAC-deep sedation (MAC-DS).
In a prospective interventional study, we included patients with a Richmond Assessment Sedation Score (RASS) of 0 without any sedation. We stepwise increased sevoflurane concentration level before assessing for deep sedation (RASS ≤ −3). MAC-DS was defined as the minimal sevoflurane MAC fraction or sevoflurane expiratory fraction (FeSevo) to get 90% and 95% of patients in deep sedation (MAC-DS 90 and MAC-DS 95, respectively).
Between June and November 2014, 30 patients were included (median age = 60 years [interquartile range: 47–69]). Increasing sevoflurane MAC was correlated with a decrease in RASS values (r = −0.83, P < 0.001). MAC-DS 90 and MAC-DS 95 were achieved at 0.42 MAC (CI 95 [0.38–0.46]) and 0.46 MAC (CI 95 [0.42–0.51]), respectively. FeSevo to achieve MAC-DS 90 and MAC-DS 95 was 0.72 (CI 95 [0.65–0.79]) and 0.80 (CI 95 [0.72–0.89]), respectively.
In this physiological study involving 30 ICU patients, MAC-DS, end-tidal sevoflurane concentration to get 95% of patients in deep sedation determined over more than 500 observations, is achieved at 0.8% of expired fraction of sevoflurane or at 0.5 age-adjusted MAC.

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SedationState of the art: Sedation concepts with volatile anesthetics in critically Ill patients

Abstract

Introduction

Section snippets

Protective effects of volatile anesthetics

Technical possibilities of inhalative sedation

Options for residual gas scavenging

Inhalative sedation—clinical experience

Limitations

Conclusion

Lancet.

Crit Care Clin

Br J Anaesth

Brain Res

Br J Anaesth

Br J Anaesth

Best Pract Res Clin Anaesthesiol

Chest

Practice of sedation and analgesia in German intensive care units: results of a national survey

Crit Care

Decreased duration of mechanical ventilation when comparing analgesia-based sedation using remifentanil with standard hypnotic-based sedation for up to 10 days in intensive care unit patients: a randomised trial

Crit Care

The use of sedative agents in critically ill patients

Drugs

Complications of sedation with midazolam in the intensive care unit and a comparison with other sedative regimens

Crit Care Med

Comparison of recovery profile after ambulatory anesthesia with propofol, isoflurane, sevoflurane and desflurane: a systematic review

Anesth Analg

Organprotektion durch volatile Anästhetika

Anästhesiologie und Intensivmedizin

Einbau von Narkosegasvaporen in der Herz-Lungen- Maschine

Anästh Intensivmed

Sevoflurane improves neurological outcome after incomplete cerebral ischaemia in rats

Br J Anaessth

Technische Vorraussetzungen für die Langzeitsedierung mit volatilen Anästhetika (Isofluran)

Use of sevoflurane sedation by the AnaConDa™((R)) device as an adjunct to extubation in a pediatric burn patient

Burns

Three cases of PICU sedation with isoflurane delivered by the ‘AnaConDa™’

Paediatr Anaesth

Criteria for a recommended standard: occupational exposure to anesthetic gases and vapors

Ambient isoflurane pollution and isoflurane consumption during intensive care unit sedation with the Anesthetic Conserving Device

Crit Care Med

Exposure of intensive care personnel to isoflurane in long-term sedation

Anasthesiol Intensivmed Notfallmed Schmerzther

Erste klinische Erfahrungen in der Langzeitsedierung mit Isofluran

Sedierung mit Isofluran unter pulmonalen und hämodynamischen Aspekten

Isoflurane compared with midazolam for sedation in the intensive care unit

BMJ

Sedation
State of the art: Sedation concepts with volatile anesthetics in critically Ill patients

Use of sevoflurane sedation by the AnaConDa^™((R)) device as an adjunct to extubation in a pediatric burn patient

Three cases of PICU sedation with isoflurane delivered by the ‘AnaConDa^™’