Malek J.¹, Simankova E¹, Jandova J.¹, Broz L.²

¹Clinic of Anaesthesiology and Resuscitation and ²Clinic of Burns Medicine,
3^rd School of Medicine, Charles .University, Prague, Czech Republic

SUMMARY. The objectives of this open-perspective clinical study were to test the effect of a new type of anaesthesia using sevofluran during surgical treatment of patients with burns, and to compare it with that of ketamin, at present the most frequently used anaesthetic. The study, conceived as a pilot study, was performed on 10 paediatric and 8 adult patients with 2"d degree burns covering between 7% and 35% of body surface. Owing to highly significant differences in parameters in favour of sevofluran, it was recommended by our ethical committee not to increase the number of patients. The parameters considered were ease of induction, undesirable effects, span of time before oral administration of liquids. Daily uptake of energy was measured for both types of anaesthetics in another group of 10 patients. In adult patients the two anaesthetics, ketamin versus sevofluran, differed in terms of incidence of unrest during surgery (ketamin 50% vs. sevofluran 0%, p<0.05), time between end of surgery and return to full consciousness (11.3 min. vs. 2.7 min. p< 0.001), post-surgical inhibition (75% vs. 0%, p<0.01) psychomimetic reactions after surgery (50% vs. 0%, p<0.05), time until first intake of liquids (86.7 min. vs. 8.5 min, p<0.001), and mobilisation (110.8 min. vs. 17 min., p<0.001). In paedriatic patients, differences in speed of onset of anaesthesia (216 sec. vs. 66 sec., p<0.001) and time until first uptake of liquids (75 min. vs. 22 min., p<0.001) were statistically significant. Apart from problems associated with anesthesia, another considerable advantage of the new anaesthetic sevofluran was a significantly increased uptake of calories after use than was the case after ketamin (1645 kJ higher on the average, p<0.05). Based on these results, sevofluran was introduced to burns surgery as a routine anaesthetic.

ZUSAMMENFASSUNG

Die neue Anasthesie mit Sevofluran verbessert per- and postoperativer Verlauf chirurgischer Behandlung verbrannter Patienten

Malek J, Slmankova E, Jandova J, Broi L.

Im Rahmen dieser klinischen Studie wurde eine neue Anasthesie mit Sevofluran mit der konventionellen Anasthesie mit Ketamin verglichen. Zehn jugendliche and acht erwachsene Patienten mit Verbrennungen der zweiten Stufe im Umfang von 7% bis 35% der Korperoberflache wurden in die Studie einbezogen. Geschwindigkeit der Einfiihrung in die, die Nebenwirkungen and die Zeit der peroralen Flussigkeitaufnahme wurden bewertet. Bei den anderen zehn Patienten wurde die tagliche Energieaufnahme gemessen. Bei erwachsenen Patienten wurden folgende signifikante Unterschiede zwischen Anasthesie mit Ketamin and Sevotluran gefunden: Auflcommen der Unruhe wahrend der Operation (50% vs. 0°/0, p<0.05), die Zeit der Ruckkehr ins Bewusstsein nach dem Anasthesieende (11.3 min vs. 2.7 min, p<0.001), postoperative Hemmung (75°/o vs. 0°/0, p<0.01), psychomimetische Reaktionen nach der Operation (50% vs. 0%, p<0.05), die Zeit des ersten Trinkens (86.7 min vs. 8.5 min, p<0.001) and die Zeit der Mobilisation (110.8 min vs. 17 min, p<0.001). Bei jugendlichen Patienten wurden folgende signifikanre Unterschiede gefunden: Geschwindigkeit der Einfuhrung in die Anasthesie (216 s vs. 66 s, p<0.001) and die Zeit des ersten Trinkens (75 min vs. 22 min, p<0.001). Der wichtige Vorzug neuer Methode liegt auch in der hoheren Energieaufnahme nach der Anasthesie mit Sevofluran (im Durschnitt um 1645 kJ h6her, p<0.05). Angesichts dieser Ergebnisse wurde Anasthesie mit Sevofluran in die Behandlung von Patienten mit Verbrennungen eingef0hrt

Key words: treatment of burns, anaesthesia of burn casualties, post-surgical course

Anaesthesia of patients with extensive burns differs considerably from other planned procedures (Sturma, 1990). In addition to the common triad of anamnesis, analgesia and vegetative stabilisation, it is necessary to consider many other factors (Konigova 1990). Disturbance of functions of the liver and other parenchymatous organs develop sooner or later in severely burned patients, in addition to an increased level of katecholamines. These patients have increased oxygen consumption and thus respiratory inhibition due either to an anaesthetic or analgesic increases the damage caused by the accident. A disadvantage of the so-called heavy premedication using high doses of long-term effective opioids is the disorientation of patients over a long period after surgery and an inability to ingest liquids and rehabilitate. Breathing is slow and superficial, and expectoration is low. Since the surgery is very painful, anaesthesia has to be highly effective and readily controllable in order to provide adequate analgesia, suppress stress caused by surgery and enable early recovery. Therefore a combination of opioid (fentamyl), anaesthetic (ketamin) and sedative (diazepam or midazolam) (Sturma 1999, Maldini 1996) is frequently used.

Although this combination has several positive effects; there are certain problems such as high doses (Miller 1990, Bertin-Maghit 1995, Group of authors 1994). The effects of opioids have been described earlier. Ketamin is known to cause clono- and even laryngospasms, muscle hypertonus. A frequent complication is caused by psychomimetic effects, because these have to be treated with high doses of benzodiazepin, which again deepen post-surgical inhibition (Group of authors 1994, Escarment 1995). The sympathomimetic properties of ketamin stimulate circulation and lead to an increased uptake of oxygen by myocardium.

Anaesthesia of paediatric patients poses a specific problem. In most cases of extensive burns of children we use total anaesthesia, whereas analgesia would be used in similar adult cases. This means repeated anaesthesias (generally every second day) and again during reconstruction. There are numerous problems associated with repeated anaesthesias, such as their effect on parenchymatous organs, nutrition (enforced starvation interferes with oral uptake of food and liquids). Another problem is avoidance of repeated tracheal intubation and the use of muscle relaxants, frequently difficult intravenous access and fear of syringes.

Inhalation anaesthesia is generally convenient for dressing and treatment of smaller burns areas; for small children, it may be a matter of choice (Judkins, 1996); on the other hand, its disadvantage is a rather limited choice of suitable substances. Repeated anaesthesias with halotan may cause liver damage (Ray et al., 1999) although hepatotoxicity is less likely to occur in children than it is in adults (Ray et al., 1999). Isofluran and entluran have a pungent, irritant smell and are therefore not suitable.

Intravenous anaesthesia is convenient in terms of its fast induction and easy management. It is not suitable for repeated venous puncture, except for anaesthetic purposes in cases when long-term access to the vein would not be needed. It is often extremely difficult to insert a cannula into a child's vena; merely holding down its arm before puncture may trigger hysterics or cause horror (Fradet et al., 1990). For these reasons, the method used most commonly with children is intramuscular administration of ketamin (Ward et al., 1976, Cote, 1992, Judkins, 1996). The use of ketamin has its disadvantage both in adults and children in that it provokes psychomimetic reactions and evokes disagreeable dreams appearing as late as several weeks after the last administration of anaesthesia (Meyers et al., 1978). Another problem arising from its use is phobic fear of any kind of syringe, difficulty in managing depth of anaesthesia and long-term sedation after repeated doses. In addition, this is potentiated by benzodiazepins administered together with ketamin to suppress its undesirable effect.

An alternative to intravenous and intramuscular techniques used both for adults and children is inhalation anaesthesia. With regard to the previously mentioned damage to parenchymatous organs and problems with induction by inhalation, the choice of anaesthetics is severely limited. Sevofluran appears to be optimal in its effect; this is a new inhalation anaesthetic. It has no irritant smell, is well tolerated both by adults and children, and its induction speed is comparable with that of intravenous administration, even when used with adults (Smith, 1995). Owing to its low solubility in blood (coefficient blood/gas 0.69), it is readily controllable, waking is easy and quick. Among the known undesirable effects are lower ventilation response to C02 and lower blood pressure through vasodilatation - but without changes in heart activity. It does not sensibilitise myocardium to the effect of katecholamins, which are metabolized by only about 2%. Therefore it may be the appropriate substance for inhalation anaesthesia with a mask, except for patients with burns on their face and head. We have not found any reference to sevofluran in professional literature (MEDLINE). This situation initiated our study on sevofluran as an initial inhalation anaesthetic and during surgery in the treatment of burns in children and adults, comparing the results with ketamine anaesthesia, an anaesthetic still commonly used both during and after surgery.

1. SEVOFLURAN IN ANAESTHESIA OF BURNED CHILDREN

1.1 Study group and methods

Having obtained permission from both our ethical committee and legal representatives of the children for our study group, we selected 10 children with burns (degree 2, coverage 7-20% of body surface except head and face) aged between 1.5 and 7 years, expected be submitted to repeated anaesthesias. In order to avoid interindividual differences in tolerance for anaesthetics and psychic reaction to stress during surgery, we studied identical patients during repeated anaesthesias in using a method of accidental choice, i.e. first intramuscular ketamin (K) anaesthesia or inhalation sevofluran (S) anaesthesia, and we alternated both methods regularly for as long as the patients required total anaesthesia.

Premediactiion for K was midazolan (0.4 mg/kg), for S tramadol (1 mg), always 30 min. before induction of anaesthesia. Induction with type K was ketamin 5 mg/kg i.m. followed by a mixture of oxygen and dinitrogen oxide, ratio 1:2, through a mask. Whenever required by prolonged surgery, induction anaesthesia is followed by introducing to the peripheral vein through a canula a required quantity of boluses of ketamin, midazol and fentanyl. Induction with S consisted of a mixture of oxygen and dinotrogen oxide (1:1) and sevofluran at 8% concentration for 2 min. and 4% concentration for another 4 min., then at required concentration (roughly 2%). The indications for introducting a canula to the peripheral vein were identical to K. One-way respiratory systems (Jackson, Reese, Bain) were employed in both types of anaesthesia for inhaling anaesthetic mixtures. In addition to normal monitoring during surgery, notes were made about induction (1-child at rest, 2-faint weeping, 3-physical resistance), time of start of anaesthesia, time at which surgeon can start treatment, complications during surgery (haemodynamic changes, laryngo n. bronchospasm), speed of wakening, from end of surgery up to spontaneous opening of eyes or upon request (older children), post-operational course (1-without complications, 2-moderate problems without pharmacological intervention, 3-serious problems (unrest, pain) need for pharmacological treatment, time until first intake of liquid, i.e. time of being fully awake with all protective reflexes and capable of accepting food P.O.

Results were evaluated statistically with the Wilcoxon test.

1.2. Results

Results are shown in Table 1. There were no statistically significant differences in these parameters: easiness of induction, speed of waking up, post-operational course. Highly statistically significant differences were found between time of onset of anaesthesia and time of first intake of drink (in favour of sevofluran). Among the undesirable effects were 2x tachycardia (ketamin group), lx short-lived laryngospasm, 1x inadequate post-operational analgesia (sevofluran group). Although muscle relaxation was slightly higher with sevofluran than with ketamin, this made it necessary to pay more attention to possible blockage of respiratory routes.

1.3. Discussion

Like other authors (Smith et a1.,1996, Rieger et a1.,1999), we observed a very short and agreeable induction. Contrary to expectations, there was no statistically significant difference between intramuscular ketamin and inhalation induction of sevofluran. Apparently, this may be ascribed mainly to premedication with midazolam restricting pre-operational stress to a remarkable degree (Holm-Knudsen et al., 1998, Funk et al., 2000). With regard to the fact that sevofluran has no analgetic properties, we used orally administered tramadol instead of midazol for premedication of group S, in order to ensure adequate post-operational analgesia. Contrary to the aforementioned authors, we did not observe any statistically significant differences in the time of waking. There may be several explanations. Concomitant administration of oxygen and dinitrate oxide in group K potentiates analgesia and anaesthesia; elimination of dinitrate oxide quickens waking. Another possibility may have been unsuitable choice of waking criteria, with regard to the fact that ketamin causes dissociation anaesthesia, and spontaneous opening of eyes or reaction to verbal call does not indicate the state of being completely awake. This explanation is also supported by the long latency preventing safe oral administration of liquid to children after ketamin anaesthesia. Another possibility: sevofluran supply was cut off at the end of surgery for fear of early waking. Whatever the reason, the time from the end of surgery to arrival of the child in the ward was of little importance in both groups and did not prolong times of the surgical programme. Differences in post-surgical course were insignificant, evidently due to the fact that psychomimetic reactions after ketamin are not very frequent in children and, in addition to that, their incidence is further decreased by premedication with midazolam. Unlike Holzki (1999) and Lapin et al. (1999), we did not observe either confusion or agitation flowing anaesthesia with sevofluran. It is difficult to decide whether the reason was premeditation with tramadol or the composition of the study group. Lapin et al. (1999) described an incidence of excitation in up to 67% out of a group of 100 children that had not been premedidated. This high percentage indicates that an opioid present in premedication of our study group must evidently have suppressed excitation. With regard to a quick waking up after sevofluran, adequate analgesia after surgery is an absolute necessity. We obtained satisfactory results with oral administration of tramadol (1 mg/kg).

A frequently discussed question is the cost of sevofluran. Anaesthesia of children and short interventions require a great intake of fresh anaesthetic mixture which increases greatly consumption of sevofluran. Our study group is too small for a detailed economic balance. Roughly speaking, sevofluran is about 10x more expensive than ketamin. Before making a definitive conclusion, we shall have to consider the faster and simpler induction of anaesthesia, and shortening of postsurgical supervision, in addition to other factors that are difficult to express financially - such as lower invasiveness, more frequent oral intake of liquid and others.

1.4. Conclusion of paediatric section

Sevofluran proved satisfactory in paediatric practice when used in dressing of burns. In contrast to commonly used intramuscular anaesthesia with ketamin, its induction is statistically significantly shorter, and so is the period before oral intake of liquids. There was no difference either in ease of induction and speed of waking or occurrence of pre- and post-surgical complications.

2. SEVOFLUR,AN IN ANAESTHESIA OF ADULT BURNS PATIENTS

2.1. Patients and methods.

Having received consent from both ethical committee and informed patients, we established a study group composed of 8 adult patients with burns of grade 2 and 3 covering between 15% and 35% of body surface, for whom repeated anesthesia was indicated. Using the method of incidental selection (envelope technique) sevofluran (S) was used as the first anaesthetic, ketamin (K) as the second, then they both alternated regularly for as long as total anaesthesia was required. By alternating the two types of anaesthetics within the same group of patients, we minimalised interindividual differences in quantity of anaesthetics and the incidence of certain undesirable effects, particularly with ketamin.

Premeditation was identical with both types of anaesthetics: pethidin 50-100 mg +atropin 0.5-1 mg i.m. Ketamin (K) anaesthesia: induction with ketamin 1.5 mg/kg ± diazepam 5 mg i.v. or ketamin 150-300 mg+midazolam 5 mg i.m. N20 and 02 (ratio 2:1) through facial mask, ketamin, 1/4 of induction dose, was added whenever necessary.

Sevofluran (S) anaesthesia: after oxygenation (6 1/min. over 5 min.), circuit of Anestar N8, an anaesthiological equipment (Chirana) was prefilled with a mixture of oxygen and dinitrogen oxide (1:2) and sevofluran (8% concentration) (evaporator Penlon, Sigmas Elite, Intermed.). The patient was asked to expire maximally; then the mask was placed on his face and he was asked again to breathe in maximally and continue breathing in and out until loss of consciousness. At that time, inflow of gas mixtures was 6 1/min. After loss of ciliary reflex, input of mixture was decreased to 3 1/min. with a simultaneous decrease in sevofluran concentration to 4% and then after 2 minutes gradually down to final 2%.

All patients were monitored for peripheral blood saturation with oxygen, noninvasive blood pressure, pulse frequency (Schiller equipment).

Criteria for release of patient from operating theatre to standard ward: capacity of answering a call, simple verbal communication, absence of serious undesirable effects:

Parameters observed:

• In connection with induction-period until loss of consciousness, ease of induction by a 4grade scale (I-necessary to do it another way, IIcomplications that have to be treated pharmacologically, III-mild complications, IV-without difficulties), spasm of respiratory routes.
• In connection with course of anaesthesia: brachycardia: pulse frequency (P below 50/min), tachycardia (P above 100/min), changes in blood pressure by more than 30% of initial value, need for supporting manual ventilation sing a mask, unrest/unsatisfactory effect.
• In connection with the end of anaesthesia and post-surgery course: time between end of surgery and waking, pain after surgery, psychomotory unrest, somnolescence, nausea, vomiting, time up to first intake of drink, time up to spontaneous motility.

Statistical evaluation of results using chisquare and Whitney test.

2.2. Results

There were no differences between the two anaesthetics in time of duration of anaesthesia and surgery. For other results and their evaluation see tables.

Note: all evaluating scales explained under methodology. If not referred to differently, values did not differ statistically from each other.

Abbreviations and symbols used in text: *p<0.05, **p<0.01, ***p<0,001

2.3 Discussion

Our study, although conceived as a pilot study with a small number of patients, demonstrated quite clearly that sevofluran was the anaesthetic of choice for adult patients with burns requiring surgery for whom lung respiration is not indicted. Although faster waking using sevofluran was statistically significant, it was of little importance in the clinic. This also applies to undesirable effects. Among its primary advantages are an absence of persistent sedation after surgery and an early intake of liquid, in addition to fast mobilization of the patient. An enteric mode of providing nutrition has a number of advantages (Pachl, 1999). There is no need for inserting a catheter into the central vein, which carries risks of septic complications, while absorption of nutrients in the portal system supports metabolism and provides for an improved stability of gastro-intestinal barrier. It lessens risk of ulceration in the area of gastrointestinal tract. Repeated anaesthesias (sometimes every second day) at present mean an interruption of oral intake for 12 and more hours. Regarded from this point of view, there can be no doubt that early oral intake of liquid as demonstrated in the last part of our study is of great advantage. The fact that the patient is awake and able to cooperate is a further advantage of sevofluran. Other advantages, although not examined directly, are these: easy induction of anaesthesia to patients with restricted access to veinal bloodstream, where venopuncture serves just the purpose of performing total anaesthesia. Although intramuscular introduction of ketamin may be possible, it has the disadvantage of retarded onset of its effect and is less readily controllable than when introduced intervenously. For the purpose of our study, this was performed in all patients before induction or after inserting a canula into the peripheral vein for treatment of possible complications that may occur with an unknown new technique. However, it seems that with sevofluran venopuncture may not be necessary in patients with not very extensive burns. With adequate premediction, an incidence of pain after surgery need not be significant. A disadvantage of sevofluran is the fact that it cannot be used in patients with burns on their face or head.

2.4 Conclusion of study of adult patients

Sevofluran was found satisfactory for inducing and controlling anaesthesia while dressing burns in adult patients. Among its primary advantages are these: fast return to full consciousness, the possibility of early oral intake of liquids, and early mobilization. Among parameters that have not been tested is the possible exclusion of venous puncture in patients with extensive burns, which is often painful and difficult to perform. Values of increased consumption of fentanyl during surgery and a higher incidence of pains after surgery in group S did not attain statistical significance. Its disadvantage is its limitation to patients who can support use of a facial mask owing to the character of damage and more difficult maintenance of unclogged respiratory routes.

3. MEASURING ENERGY UPTAKE

3.1 Methods

Energy uptake was measured in 10 patients at day of surgery between 0 and 24 hrs. A record of exact quantity of energy uptake (in gr) was kept by the nurse in addition to composition of solid and liquid food intake by the patient on the day of surgery. Results were evaluated by a software programme called Ostrasoft and statistically evaluated with sign test and Wilcoxon tests.

3.2 Results

In 9 out of 10 patients, daily uptake of energy was higher in patients with S anaesthesia than in those with K anaesthesia. Average daily energy uptake was 1645±2534.5 kJ more in patients after S- than after K anaesthesia. The result was statistically significant with sign test, almost significant with Wilcoxon test (p=0.053).

3.3 Discussion

Energy uptake is higher in persons with burns. The metabolic response of these patients is the highest of all. Hypermetabolism decreases after fading of shock; it attains its peak between day 7 and 12 after the accident. In patients with extensive burns trauma, this peak attains twice its normal value (Wilmore et al., 1997). Energy output of patients with extensive burns covering up to 30% of body surface is equally high as in patients in deep trauma, sepsis and respiratory failure (Wilmore et al. 1997). The importance of enteric introduction of nutrition was emphasized earlier. According to Pachl (1999), it has numerous advantages. There is no need to insert a catheter into the central vein, which carries risk of septic complications: absorption of nutrition by portal system supports metabolic processes in the area of the splachnoderm and improves stability of gatrointestinal barrier. Enteric nutrition decreases the danger of ulceration in the area of the gastrointestinal tract.

Measuring uptake of energy at normal, p.o. nutrition; apart from the time factor of starvation, it influences a number of variables such as present state of mind, disturbing situations, pain, temperature etc. Therefore we are unable to explain why just. one out of 10 patients of our experimental group answered to ketamin anaesthesis with am increased uptake of energy. In our opinion, an increased uptake of energy at the day of surgery may be ascribed to a shorter period of starvation before sevofluran induction.

3.4 Conclusions of energy uptake measurements

Sevofluran anaesthesia is marked by a statistically significant increase in energy uptake, which is higher than with ketamin anaesthesia. In spite of numerous factors involved, a plausible explanation appears to be that the interval before the first intake of food p.o. appears to shorter than with ketamin anaesthesia.

4. FINAL CONCLUSIONS

Using sevofluran as an anaesthetic in burns cases is a matter of choice, whenever it is possible to use an inhalation anaesthesia. In comparison with ketamin, one primary advantage of sevofluran is its simpler and shorter induction to anaesthesia, together with avoidance of various venous punctures and intramuscular insertions, especially with children. It is easy to control depth of anaesthesia, waking is faster, there are fewer complications during and after surgery, often there is an early oral intake of nutrition resulting in a higher uptake of energy on day of surgery. Its relative disadvantage is a limited use; it cannot be used with cases of head and face injuries because it requires the use of a facial mask. Another disadvantage is high costs.

This study was supported by grant IGA MZ 6116-2

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