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San Sebastian 2004 Session 1-1 |
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Inhalative sedation in the ICU / Sedación inhalatoria en cuidados intensivos.
Dr. Andreas Meiser, Bochum, Germany.
Abstract
Sedation of ventilated patients in the ICU faces many problems. In a group of 150 ICU patients that had been ventilated for longer than 48 h Rotondi and coll. reported that 50% remembered the endotracheal tube in place. Common other experiences were “pain, fear, anxiety, lack of sleep, feeling tense, inability to speak/communicate, lack of control, nightmares, and loneliness”. This was in the United States and in other countries things are no better. In Germany, Schelling and coll. reported the occurrence of posttraumatic stress disorder (PTSD) in 27% of survivors of an adult respiratory distress syndrome. On the other hand Kress et al. could show that “daily interruptions of sedative infusions…” reduced the duration of mechanical ventilation from 7 to 5 days and the mean ICU stay from 10 to 6.5 days. Their patients were closely watched by a study observer when the infusions were stopped, and the sedative regimens were restarted as soon as the patients showed signs of wakefullness. The reduction in ICU days also underlines the economic importance of their finding. In a follow up study, the same group of authors showed that the daily interruption of sedation did not result in an adverse psychological outcome but in fact “reduced symptoms of PTSD”. The message is not that we generally oversedate patients, but that intravenous sedation is difficult to control. In addition lack of manpower quite often leads to a lack of attention to the patient and patients left alone may have psycholgically very stressful experiences.
Propofol, a relatively short acting intravenous sedative, has become very popular in many countries. Its use for ICU sedation in children had already been questioned in 1992 by Parke and coworkers in Great Britain who reported five deaths after “metabolic acidosis and fatal myocardial failure” attributed to high dose propofol infusions. A similar report for adults was published 2001 by Cremer and coworkers in Belgium. The authors suggest that propofol for ICU sedation should be used only at dosages below 5 mg/kg/h. For many patients on longer term ventilation this is not enough unless high doses of other drugs e.g. opioids are used.
Sedation with intravenous drugs seems to have severe disadvantages and side effects. For midazolam, a short acting benzodiazepine, quick onset of tolerance and a ceiling effect are characteristic. Opioids depress respiration and intestinal motility. This interferes with current therapeutic concepts like early enteral feeding and augmentation of spontaneous breathing in patients ventilated mechanically. For these reasons we believe it is worth looking for alternative treatment options.
Inhalational sedation with Isoflurane has become popular about 15 years ago and is still used in some hospitals for instance to treat severe status asthmaticus. Kong and coworkers performed the first randomized controlled trial comparing Isoflurane with midazolam for ICU sedation and Kong published extensively about the subject. The reason why isoflurane sedation did not gain more widespread acceptance may be of technical and educational nature. Generally ICU staff is not familiar with the handling of volatile anaesthetics (VA), the expiratory gases from the patient need to be scavenged and there must be a way to deliver VA. A normal ICU ventilator with a half open breathing circuit will lead to a high consumption of VA whereas an anaesthesia ventilator is bothersome, expensive, normally not available and usually does not allow the same ventilatory modes as an ICU ventilator.
Our group has focussed on inhalational sedation with desflurane. In a pilot study in 32 postoperative patients we could show that emergence after on average 11 h of desflurane sedation was predictably short with a narrow statistical deviation and it was independent from the age of the patients, from their weight, regular alcohol intake, from the duration of sedation and from the used endtidal fraction of desflurane (FetDesflurane).
In a randomized controlled trial with 60 patients published in the British Journal of Anaesthesia 2003, we could demonstrate the quick, predictable emergence and mental recovery after postoperative sedation with desflurane compared to propofol. We demonstrated an equal level of sedation with the Ramsay Score as well as with the Bispectral index. We did not see any desflurane associated tachycardia or hypertension probably because we used low concentrations of desflurane. In fact heart rate was more often in the normal range during sedation with desflurane. We did not see any differences in oxygenation, liver or kidney function or markers of toxicity. We found a slight but significant increase in CO-hemoglobin levels in both groups, more pronounced in the desflurane group, probably attributable to the use of a breathing circuit with a fresh gas flow of 1 L/min in both groups. Interestingly no patient after desflurane complained of nausea and none vomited. Pure drug costs were less for desflurane (95 €/24h) compared to propofol (171 €/24h).
In our latest project “augmented spontaneous breathing during inhalational sedation with desflurane in a totally closed circuit”, we studied 10 postoperative patients. We used Zeus®, a new anaesthesia ventilator from Dräger Medical, Lübeck, Germany. Zeus offers ventilatory modes comparable to an ICU ventilator, it can be used as a totally closed circuit and the system adjusts the inspiratory oxygen fraction and FetDesflurane with automatic feedback control. As opioid, we used Remifentanil at an initial dose of 50 ng/kg/min. Mechanical ventilation was reduced until the endtidal CO2 concentration rose up to 60 mmHg or until spontaneous breathing occurred. Then the remifentanil dose was reduced until the opioid breathing pattern and the endtidal CO2 concentration normalized. During awakening we followed a strict standard protocol. A sound file consisting of a compound word (e.g. motor boat) repeated 6 times was played to the patient via ear phones. Then the patient was asked to open eyes. If the patient did not wake up, FetDesflurane was reduced by 0,2 Vol% and after 5 min equilibration another sound file with a different compound word was played and so on. Breathing pattern as well as endtidal CO2 concentrations and arterial CO2 partial pressures did not change during the reduction of desflurane. Awakening was always brisk and occurred at an FetDesflurane of 2.0 Vol% (range: 1.5 – 2.6 Vol%). 9/10 patients stated their date of birth before 3 min after extubation. When asked 2 h later, no patient remembered the removal of the tracheal tubes. In addition, no patient could correctly fill in the second half of the compound words that had been played to him until extubation. We conclude that spontaneous respiration is possible under sedation with desflurane, it can be titrated by the opioid dose, and there is no explicit nor implicit memory for the time of sedation. Consumption of fresh gas was 35 litres/hour which corresponds to a continuous flow of 0.4 litres/min plus an automatic system flush of 12 litres once every hour. The consumption of Desflurane was 9.2±2.9 ml/hour and remained constant over time, resulting in drug costs of 3 €/h , which is comparable to the price of propofol sedation (4-5 €/h) .
Ventilator properties of Zeus and its automatic feedback control make inhalational sedation with Desflurane a real alternative to intravenous sedation. Circulatory and temperature regulation also function well at the concentrations used. In fact other organ systems may be less depressed than with intravenous sedation: We found an improvement in intestinal function in two patients on long term ventilation outside the study fed via nasoduodenal tubes while they were sedated with Desflurane. One patient had been sedated with Desflurane for 70 hours. Unfortunately Zeus is not licensed for stand alone use and its cost will also limit its use as an ICU ventilator in the near future. Therefore the looking for alternative ways to apply VA like desflurane in the ICU setting will need to go on.
