Volatile agents in the ICU in General

Sedating patitens undergoing mechanical ventilation in the intensive care unit- winds of change.
Kong KL. Brithish Journal of Anaesthesia Vol. 90, No. 3, p 267-269, 2003.
Editorial.

Sevoflurane sedation in the intensive care patients.
Guzman RE. et al. Poster at ESICM, October 2003.
"Introduction: Sevoflurane is an inhaled anesthetic of short acting period, brief elimination time, and minimal hepatic biodegradiation. Thus, it is an attractive agent for intensive care patients sedation who are under mechanical ventilation. The scope of this work was to determine its usefulness in medium term sedation.
Conclusions: Sevoflurane pharmacokinetics and pharmacodynamics allows its administration in Intensive Care patients without detriment in hemodynamic, respiratory, hepatic and renal function. All patients fulfilled an adequate grade of sedation and rapid wake up time. We conclude that Sevoflurane is useful in short term and medium term sedation in patients under mechanical ventilation."

Isoflurane in the treatment of asthma. Case Report.
Revell S, Greenhalgh D, Absalom SR. Anaesthesia, Vol. 43, p 477-479, 1998.
"Summary: A 22-month-old child developed severe bronchospasm. Prolonged ventilation of the lungs with isoflurane for 102 hours was used as treatment. The metabolism and fluoride levels obtained are discussed."

Rapid response to isoflurane in refractory status asthmaticus.
Rice M, et.al. Arch. Dis. Child, Vol. 78, p 395-400. Letter. 1998
"Two cases illustrate that intubation and ventilation of severe asthmatics, even in the setting of impending respiratory collapse, may result in significant deterioration despite appropriate ventilatory strategies. Early administration of isoflurane is beneficial in those children who fail to improve despite aggressive conventional and adjunctive treatment while the close temporal relationship between isoflurane administration and both clinical and biochemical improvement, suggests a rapid bronchodilatory response. Management of these patients is considerably facilitated by continuous intra-arterial blood gas analysis."

Long-term sedation with Isoflurane in postoperative intensive care in cardiac surgery.
Tanigami H, et.al. Artificial organs, Vol. 21, p 21-23, 1997.
Abstract:
"After cardiac surgery, patients often require prolonged mechanical ventilation. We studied the effectiveness and potential toxicity of isoflurane sedation in 40 patients undergoing mechanical ventilation after cardiovascular surgery. All patients who received isoflurane were well sedated by it without significant adverse effects, such as renal, hepatic, or cardiovascular dysfunction. The highest serum inorganic fluoride concentration recorded was 45 mmol/L after 98 MAC h. Patients on isoflurane recovered more rapidly and were weaned from mechanical ventilation sooner than those sedated with intravenous drugs including fentanyl/midazolam. Patients who received intravenous sedatives, but not those on isoflurane, often showed tachyphylaxis in the early stages, and some exhibited an abstinence syndrome involving nonpurposeful movements. Patients sedated with isoflurane did not show these two side effects. In conclusion, isoflurane can provide effective long-term sedation for patients after cardiovascular surgery without significant adverse effects."

Inhalational Anesthetics in the Intensive Care Unit.
Kong KL, Critical Care Clinics, Vol. 11, No. 4, 1995.
"Conclusions: The use of an inhalational agent for sedation in the ICU is not a new concept. Technological advances have overcome many of the practical difficulties with administering inhalational agents to the intensive care patient on the mechanical ventilation. The use of nitric oxide in the treatment of patients with severe adult prespiratory distress syndrome has provided another impetus for technological developments in this area. Many inhalational agents are available, but only isoflurane can be recommended. While possessing some of the properties of the ideal sedative agent for critically ill patients, it is nevertheless imperfect. In particular, its metabolism to inorganic fluoride, leading to rising concentrations of plasma fluoride levels following prolonged sedation, is a source of continuing concern. The newer agent, sevoflurane, is likely to have the same disadvantage (i.e., the potential for inorganic fluoride nephrotoxicity with prolonged exposures). Whether desflurane can fulfil the promise of a better inhalational agent for intensive care sedation remains to be seen, although its cost is likely to be prohibitive."

Sedation for ventilation in the critically ill. A role for isoflurane?
Willatts SM, et.al. Anaesthesia, Vol. 49, p 422-428, 1994.
"Most ventilated patients can be sedated with an opioid infusion with sedative side-effects, possibly supplemented with bolus doses of tranquillising drugs. A few patients wo do have adequate pain relief may still require readily controlled sedation at varying depth, which can be provided by short-acting agents such as propofol or isoflurane, allowing rapid recovery.
Isoflurane is a good sedative, and avoids the problems associated with multiple intravenous infusions such as the incompatibility of solutions and the dangers associated with bolus dose administration. The main problem preventing its more widespread use is the special equipment required for its administration. The vaporizer needs to be accurate at low inspired concentrations, obviating the need for an expensive monitor to measure the inspired and expired concentration. For safety, the maximum inspired concentration should be 1%, with increments of 0.1%. For ease of use and convenience, the vaporizer should be portable and compatible with any ventilator and breathing circuit."

Prevention of atmospheric contamination during isoflurane sedation.
Coleman MA, et.al. Clinical Intensive Care, Vol. 5, p 217-220, 1994.
Abstract:
"With a view to minimising staff exposure to exhaled isoflurane which had been used for sedation, we assessed the efficacy of either activated charcoal adsorption or active or passive mechanical scavenging systems in intensive care units. Personal monitoring revealed minimal exposure of staff to the sedating agent. Infra-red analyses of ambient air rarely showed isoflurane levels greater than 26 ppm, with mean concentrations of around 1 ppm. Small spillages during vaporiser filling were of no polluting significance. The activated charcoal adsorbers functioned highly efficiently for at least 12-hours periods. With simple scavenging techniques, atmospheric isoflurane contamination during sedation with the agent remains well within an acceptable range and is unlikely to pose a health risk to nursing and medical staff."

Isoflurane sedation Ð multicentre study of 55 patients.
Appleyard TN, et.al. Clinical Intensive Care, Vol. 5, p 212-216, 1994.
Abstract:
"A multi-centre study of sedation of 55 seriously ill patients by ventilation with isoflurane at low concentrations in air-oxygen mixtures for periods up to one week was carried out in seven intensive care units. Assessments of level of sedation, breakdown to form serum inorganic fluoride and of hepatic and renal function were carried out. Side effects were uncommon and no evidence of any contribution to mortality by the agent or method was revealed. Relatively simple methods of minimising atmospheric pollution by isoflurane in the vicinity of the patients were highly effective."

Use of isoflurane for sedation in intensive care.
Breheny FX, Kendall PA. Critical Care Medicine, Vol. 20, p 1062-1064, 1993.
"Isoflurane is a fluorinated ether that is closely related to enflurane. It has a low blood gas coefficient such that alterations in the concentration administered rapidly result in changes in the depth of anesthesia or sedation. Although primarily used as an anesthetic, isoflurane has many of the desirable properties of an ideal sedative agent for use in an ICU. We report the prolonged use of isoflurane in three critically ill patients."

Prolonged administration of Isoflurane to paediatric patients during mechanical ventilation.
Arnold JH, et.al. Pediatric Anesthesia, Vol. 76, p 520-6, 1993.
"Summary: We undertook a prospective study of the effectiveness and potential toxicities of isoflurane sedation in pediatric patients undergoing mechanical ventilation. All patients undergoing mechanical ventilation who required large doses of opioids for sedation were considered eligible. Ten patients received continuous isoflurane sedation for a mean duration of 131 minimum alveolar concentration (MAC)-hours. The mean peak inorganic fluoride (F-) concentration was 11.0 mM and the highest F-concentration was 26.1 mM after 441 MAC-hours. Only one patient had a measured F-concentration greater than 20 mM. No abnormalities were noted in serum creatinine or osmolality. Creatinine clearances were available for five patients who received a mean of 193 MAC-hours of isoflurane, and only one patient ha a persistent decrease from baseline of more than 20%. Five patients demonstrated an abstinence syndrome, which consisted of nonpurposeful movements and extreme agitation. All of these patients had received at least 70 MAC-hours of isoflurane. Our experience indicates that isoflurane can effectively provide sedation to pediatric patients for prolonged periods without significant adverse effects on cardiovascular, hepatic, or renal function."

Isoflurane and propofol for long-term sedation in the intensive care unit.
Millane TA, et.al. Anaesthesia, Vol. 47, p 768-774, 1992.
"Summary: Propofol and isoflurane have been reported recently to offer better sedation than alternative agents in patients who require long-term ventilation in the Intensive Care Unit. This is the first report of a direct comparison between propofol and isoflurane. Twenty-four patients predicted to require artificial ventilation for at least 48 h were entered into a randomised crossover study to monitor sedation quality and time to recovery from sedation. There were no significant differences between the two agents in either end-point, with over 95% optimal sedation achieved by the use of each drug. Few adverse events were noted. Technological advances in the administration of volatile agents as long-term sedatives in the Intensive Care Unit may facilitate their more widespread use."

Isoflurane for prolonged sedation in the intensive care unit; efficacy and safety.
Spencer EM, Willatts SM. Intensive Care Medicine, Vol. 18, p 415-421, 1992.
Abstract:
"Objective: To compare isoflurane with midazolam for prolonged sedation in ventilated patients.
Measurements and results: Measurements were made of haemodynamic, respiratory and biochemical variables regularly during the period of sedation and for a week after stopping the sedative agent. There was no difference in any of the physiological or biochemical variables recorded between the two groups. Patients sedated with isoflurane recovered more rapidly and were weaned from mechanical ventilation sooner than those sedated with midazolam.
Conclusions: Isoflurane is a useful agent for prolonged sedation of ventilated patients and does not have any adverse effect on the cardiorespiratory system or on hepatic, renal or adrenal function."

Plasma inorganic fluoride concentrations during and after prolonged (>24 h) Isoflurane sedation: Effect on renal function.
Spencer EM, et.al., Anesthesia & Analgesia, Vol. 73, p 731-737, 1991.
"Summary: We studied the effect of prolonged sedation (>24 h) with isoflurane on plasma inorganic fluoride concentration and renal function in 60 critically ill patients allocated randomly to receive either isoflurane or midazolam for sedation. In the isoflurane group, plasma fluoride increased from a mean concentration of 3.1 mmol/L to 20.0 mmol/L at the end of sedation, continued to increase to a peak of 25.3 mmol/L 16 h later, and then decreased exponentially to reach normal levels by the fifth day. In the midazolam group, the plasma fluoride increased from a mean concentration of 4.2 mmol/l to a peak of 6.8 mmol/L 12 h after starting the sedation and then decreased toward normal. Serum and urinary electrolytes, urine osmolality, and creatinine clearance during and after sedation were similar in the two groups. Isoflurane sedation was associated with an increase in plasma fluoride concentration without any clinical deterioration of renal function."

Isoflurane Therapy for Status Asthmaticus in Children and Adults.
Jonston RG, et.al. Chest, Vol. 97, p 698-701, 1990.
"Two adults and two children with life-threatening asthma refractory to maximal standard therapy were treated with the inhalational anesthetic agent isoflurane. In each case, the temporal response to the initiation of therapy was striking. All patients survived and none experienced adverse reactions attributable to the drug. Rapid therapeutic benefit, minimal side effects, absence of cumulative toxicity, and ease of administration are factors supporting the use of isoflurane for patients with severe asthma."

Inorganic fluoride concentration after long-term sedan with Isoflurane.
Osborne MA, et.al. Intensive Care Medicine, Vol. 76, p 1277-1280, 1989.
Abstract:
"We report on five patients in whom long-term sedation with isoflurane for up to 7 days was used successfully. Serum inorganic fluoride concentrations were measured daily. The concentrations ranged from 12 mmol 1-1 to 29 mmol 1-1. These were well below the described renal toxic level of 50 mmol 1-1. There was no deterioration in renal function attributable to the use of isoflurane."

Isoflurane compared with Midazolam for sedation in the intensive care unit.
Kong KL, et.al. British Medical Journal of Anaesthesia, Vol. 90, p 267-268, 1989.
Abstract:
"Objective: To compare isoflurane with midazolam for sedation of ventilated patients.
Main results: Isoflurane produced satisfactory sedation for a greater proportion of time than midazolam, and patients sedated with isoflurane recovered more rapidly from sedation.
Conclusion: Isoflurane is a promising alternative technique for sedation of ventilated patients in the intensive care unit."

Prolonged isoflurane anesthesia in status asthmaticus.
Bierman MI, et.al. Critical Care Medicine, Vol. 14, No. 9, p 823-533, 1986.
"We report a case of status asthmaticus that was unresponsive to the usual agents. The use of an inhalational anesthetic agent allowed us to ventilate the patient with lower inspiratory pressures; however, lasting improvement did not occur until she mobilized large quantities of secretions. To our knowledge, this is the first clinical report on the use of isoflurane anesthesia to treat severe asthma. Despite prolonged administration, there were no significant side-effects. This case demonstrates both the benefits and limitations of such therapy."