Alfentanil

Total intravenous anesthesia (TNA) is a useful technique in precarious situations in which anesthesia ventilators and medical gas can be difficult to obtain. The aim of the study is to compare TNA technique using a simplified infusion scheme for propofol and alfentanil mixed together (45 ml of propofol 1% and 2,500 mug of alfentanil in a 50-ml syringe) with an inhalational anesthetic technique (isoflurane/N^sub 2^O, sufentanil). Thirty-two American Society of Anesthesiologists physical status I patients undergoing orthopedic surgery were studied. Intubation conditions and hemodynamic responses to intubation were comparable in the two groups. Only patients receiving TNA had responses to surgery. In the TNA group, time to extubation was shorter (16= 5 vs. 25/- 7 minutes) and postoperative requirement for morphine was lower (6.2% vs. 25%) than in the inhalation group (p

Introduction

In war, anesthetic technique must take into account field conditions. In military anesthesia, medical gas (volatile anesthetics, nitrous oxide) can be difficult to obtain, and their choice is limited. The availability of anesthesia ventilators and vaporizers is uncertain. Conditions in a field hospital can be extreme in terms of temperature and space.

Two kinds of patients must be cared for. Major trauma patients are outnumbered by patients with superficial trauma, fractures, fatalities, peripheral gunshots, and limb injuries.1 In such cases, anesthesia must provide rapid recovery and efficient postoperative analgesia for early evacuation.

Total intravenous anesthesia (TIVA) answers the constraints of precarious material situations and has been used successfully in war conditions.2 TIVA with two short-lasting agents such as propofol and alfentanil presents further advantages: rapid awakening, efficacy for both ambulatory surgery3 and major procedures,4,5 induction and maintenance with the same agents, and reliability with a simple ventilatory device without nitrous oxides During the Persian Gulf War, four cases of battlefield casualties anesthetized with propofol and alfentanil mixed together in a single syringe were reported.7 Even though the mixture of anesthetic agents was abandoned years ago in Western countries, this technique might be useful under field conditions. The present study tried to improve this technique by using a simplified infusion scheme.

The aim of the study was to compare in patients without multiple injuries the safety and efficacy of a TIVA technique using a simplified infusion scheme for propofol and alfentanil mixed together, both for induction and maintenance, with an inhalational anesthetic technique.

Methods

Study Design

After ethics committee approval and written informed consent, 32 American Society of Anesthesiologists physical status I patients free of medical illness and taking no medications, aged 17 to 48 years, and undergoing elective arthroscopic knee surgery (cruciate ligaments) with use of a tourniquet were included in the study. Patients were randomly allocated to one of two groups (TNA or inhalational technique).

In the TIVA group, a mixture of 2,500 tg of alfentanil (5 ml) and 450 mg of propofol (45 ml of 1% solution) was used. The concentration of each agent in the 50-ml syringe was 50 (mu)g ml^sup -1^ alfentanil and 9 mg ml^sup -1^ propofol.

Anesthetic Technique

Preinduction Period

All patients were premedicated orally with alprazolam (0.5 mg) and hydroxyzine (100 mg) 1 to 2 hours before surgery. An intravenous cannula (18 gauge) on the forearm was used for infusion of lactated Ringer's solution (5 ml kg^sup 1^ - h^sup -1^). Before induction, 3 minutes of ventilation with 100% oxygen via a face mask was achieved. Routine monitoring included electrocardiography, noninvasive blood pressure measurement, pulse oximetry, and capnography. Neuromuscular block was monitored by accelerometry (train-of four ratio, TOF Guard, Organon-Tecknica, Turnhout, The Netherlands).

Induction Period

In the TNA group, the mixture was infused by a Graseby 3400 pump (Graseby, Watford, Herts, United Kingdom) permitting infusion at a maximum rate of 1,200 ml h^sup -1^. The induction volume of the mixture was one-third the body weight in kilograms administered over 30 to 45 seconds (i.e., 3 mg kg^sup -1^ propofol and 16.6 (mu)g kg^sup -1^ alfentanil). After mask ventilation, at the second minute a dose of 0.5 mg kg^sup -1^ atracurium was injected, and maintenance infusion was started (Table I). Tracheal intubation was performed when adequate neuromuscular block had been achieved, about 5 minutes after the beginning of induction.

In the inhalation group, anesthesia was induced with 0.5 (mu)g kg^sup -1^ sufentanil, followed by 2 mg kg^sup -1^ propofol at the first minute and 0.5 mg kg^sup -1^ atracurium at the second minute (after mask ventilation). Tracheal intubation was performed at about 5 minutes after sufentanil administration, when monitoring showed adequate muscle relaxation.

Maintenance Period

In the TIVA group, the patients' lungs were ventilated with 33% oxygen and 66% air. Sixty and 90 minutes after intubation, the infusion rate of the propofol and alfentanil mixture was decreased (Table I). In the inhalation group, ventilation was ensured with 33% oxygen, 66% nitrous oxide, and isoflurane (

All patients were monitored for insufficient analgesia, defined as an increase in systolic arterial pressure or heart rate of more than 30% of preinduction values. Insufficient analgesia was treated with a 10% increase in infusion rate in the TIVA group or with a bolus of 0.2 (mu)g kg^sup -1^ sufentanil in the inhalation group. Inadequate anesthesia, defined as movement, cough, or eye opening, was treated with a bolus of 1 mg kg^sup -1^propofol in the two groups. Bradycardia (heart rate

Recovery Period

Anesthetic agents (propofol and alfentanil or isoflurane) were discontinued at the end of skin closure, and the patients' lungs were ventilated with 100% oxygen on an open circuit. Extubation was achieved in the operating room. Patients in spontaneous ventilation with oxygen saturation (pulse oxymetry). Sp02 = 95%.

Postoperative Analgesia

After the first pain evaluation in the recovery room, an infusion of propacetamol (2 g) and ketoprofen (100 mo was initiated. A subcutaneous injection of 5 mg of morphine was added if the Visual Analog Pain Scale score (on a scale of 0-10) was 4 or higher.

Study Parameters

The hemodynamic responses to induction, intubation, and skin incision were recorded. Systolic arterial pressure (SAP) and heart rate (HR) were recorded every minute between induction and skin incision and every 5 minutes during maintenance. The quality of intubation was evaluated based on five criteria: jaw mobility, ease of facial mask ventilation, vocal cord exposure, vocal cord position, and patient movement on intubation (Table II). Delay between induction and incision, duration of surgery (incision to dressing) and of tourniquet inflation, and duration of anesthesia (induction to discontinuation of agents) were recorded. The requirement for additional boluses of sufentanil or propofol, and the changes in infusion rates, were noted. After discontinuation of all anesthetic agents, the times to response to verbal command, eyes opening, and extubation were recorded. In the recovery room, the following parameters were recorded: Visual Analog Pain Scale score 30 and 60 minutes after extubation, Ramsay's Sedation Scale score 30 and 60 minutes after extubation (Table III), morphine requirement, incidence of adverse effects (apnea, nausea, and vomiting), percent of patients who required oxygen to maintain Sp02 >= 95%, and time to discharge from the recovery room (when an Aldrete score 8 of 10 was reached).

Statistical Analysis

Student's t test was used for continuous data, and discrete variables were compared using the X test. For all tests, p

Results

Patient characteristics are summarized in Table III. The groups were similar in terms of age, weight, height, and sex distribution.

Induction and Intubation Phase

Preinduction SAP and HR were similar in both groups of patients (Table III). There was no significant difference in the time to intubation between the TIVA and the inhalation group (Table III). Patients receiving TIVA had significantly lower HR at with TNA. Patients receiving a continuous infusion of propofol and alfentanil had significantly less insufficient analgesia (treated with increases in infusion rate) than patients receiving sufentanil/isoflurane (treated with sufentanil boluses) (Table IV. During maintenance, no bradycardia or hypotension required cardiovascular treatment.

Recovery Period

The times to extubation, eyes opening, and response to verbal command were shorter in patients who received TNA (Table V). The differences in Visual Analog Pain Scale score at 30 and 60 minutes after extubation were not statistically significant (Fig. 4). An evaluation of sedation at 30 minutes after extubation (Fig. 5) showed that three patients who received TIVA ( 18.7% of that patient group) were still heavily sedated (scores of 4 and 5). Patients receiving continuous alfentanil infusion had significantly lower postoperative requirement for morphine (6.2% of patients) than patients receiving sufentanil (25% of patients). The time spent in the recovery room was not different regardless of anesthetic technique (Table V). No memorization (intraoperative recall or awareness) or other adverse events (apnea, nausea, and vomiting) were reported during the postoperative phase in either group of patients. Oxygen requirements and spontaneous breath rate in the recovery room are displayed in Table V.

Discussion

A TIVA technique is particularly well suited to anesthesia in remote locations, and its usefulness under field conditions was demonstrated long ago.9 In a disaster situation in 1984, German surgical teams used intravenous anesthesia with ketamine, which seemed preferable to inhalation techniques.9 In 1988, Restall et al. proposed a TNA technique for military surgery using ketamine, midazolam, and vecuronium mixed in a single syringe. 10 In 1996 during the war in Bosnia, the French army used a TIVA technique with propofol and ketamine in various surgical procedures.11 The main advantage of this technique was that infusion pumps replaced unavailable gas circuits, vaporizers, and nitrous oxide.

Wilson and Ridley, in 1992, were the first to describe the use in war conditions of propofol and alfentanil mixed together in a single syringe.7 In that work, they used different syringes of propofol and alfentanil for induction and the mixture only for maintenance (400 mg of propofol and 2,500 (mu)g of alfentanil in 45 ml). In contrast with their study, we administered a different mixture (450 mg of propofol and 2,500 (mu)g of alfentanil in 50 m1) for both induction and maintenance. The advantages of this technique were easy preparation and administration, reliability, and fast memorization of infusion rates by the anesthetic team. A simple ventilation device (controlled ventilation without volatiles or nitrous oxide) can be used. The TIVA technique can provide anesthesia with portable and light ventilators in the field. In the present study, orthopedic surgery was chosen because it involves important intraoperative stimulation and marked postoperative pain. Young American Society of Anesthesiologists status I patients with minor trauma, free of illness or treatment, are likely to be treated in a field military hospital. Alfentanil, with its rapid onset of action, allows for efficient intraoperative analgesia. Propofol is very useful as a short-acting anesthetic agent to provide fast recovery. Propofol infusion is not suitable for severe trauma patients or in presence of hemodynamic instability because of its cardiovascular depressant properties. A mixture of anesthetic agents does not allow a titration of alfentanil or a decrease of propofol infusion rate to provide hemodynamic stability. The aim of this investigation was to evaluate for patients without hemodynamic instability or multiple injuries the reliability of a simplified administration of propofol and alfentanil.

Our study suggests that a TIVA technique using a mixture of propofol (i.e., 3 mg kg^sup -1) and alfentanil (i.e., 16.6 (mu)g kg^sup -1^) associated with a muscle relaxant provides adequate conditions for endotracheal intubation in healthy premedicated patients without anticipated difficult laryngoscopy. Hemodynamic responses to laryngoscopy and intubation were comparable in the two groups. The same hemodynamic stability was observed during maintenance with the two techniques. Nevertheless, a higher incidence of inadequate anesthesia, defined as cough or movement during surgery, existed with TIVA. The use of our infusion rates increased the number of times the anesthetist had to intervene.

The effect compartment concentrations of propofol and alfentanil has been studied with a computer simulation program [Stanpump, S. Shafer, Stanford, CA). For all durations of infusion, effect site alfentanil concentration stayed between 80 and 100 ng ml^sup -1^. Effect site propofol concentrations were initially greater than 3.5 (mu)g m^sup -1^ and decreased to less than 3 (mu)g ml^sup -1^ after 90 minutes. This simulation could explain the higher incidence of inadequate anesthesia observed after the second change of infusion rate. Vuyk et al. determined the optimal concentrations of propofol (3.4 (mu)g ml^sup -1^) and alfentanil (90 ng ml^sup -1^) for infusion lasting more than 1 hour in patients undergoing lower abdominal surgery. 12 Our protocol is suitable in remote locations where the majority of surgical procedures last less than 90 minutes. An increase of the infusion rate could be necessary if the procedure is more than 90 minutes long.

The times to response to verbal command, extubation, and eyes opening were shorter in patients who received propofol-alfentanil, which is probably attributable to the lower level of hypnosis seen in this group. However, this was not followed by an earlier discharge from the recovery room. This TIVA technique appears to be safe in terms of postoperative respiratory depression (absence of apnea, less oxygen requirement after extubation). However, high sedation scores (>= 3) were more frequent in the TWA group (4 of 16 patients). This incidence may place these patients at increased risk during recovery under field conditions because of personnel shortage. In our study, the pain score was similar in the recovery room between the two treatment groups. Nevertheless, morphine administration was more frequently necessary in patients receiving sufentanil. The delay between the last sufentanil injection and the pain evaluation could explain the higher postoperative requirement for morphine. As in the present study, some previous studies have shown a significantly shorter time to extubation and immediate recovery with TNA with propofol-alfentanil.4,5 We did not observe the same incidence of postoperative nausea and vomiting.3 The greater incidence of this kind of adverse event in that study may have been attributable to the use of nitrous oxide with TNA for longer operations.5 For nausea and vomiting, the number of patients in our study is too small to be considered clinically important.

Despite those positive points, propofol and alfentanil are expensive and are unavailable in developing countries. Adding any product to a propofol mixture is usually not recommended because of the risk of contamination and subsequent bacterial growth. The limitation of propofol use in difficult situations is the risk of microbial contamination during preparation and storage.13 Rapid bacterial growth in an oil-based solution, particularly at extreme temperatures, necessitates strict aseptic techniques during the handling of propofol. Infectious risk factors are very important in warm countries. In all, propofol can be used in difficult situations, but aseptic techniques are necessary. The delay between the opening of propofol vials and injection must be reduced as much as possible. Unlike for many muscle relaxants, refrigerator storage is not necessary for propofol. Atracurium has the advantage of easy storage at room temperature. The electricity supply can be endangered in extreme conditions, and the number of electrical devices must be reduced as much as possible. Today, modern field hospital provide a regular supply of electricity. The use of a single syringe pump, therefore, is always possible.

Conclusion

In conclusion, in healthy premedicated patients undergoing orthopedic surgery, TIVA with simplified infusion rates of a propofol-alfentanil mixture allowed a satisfactory course of anesthesia. The main advantages are fast awakening and efficient postoperative analgesia. Without being better than the inhalational technique studied here, TNA remains a useful technique in precarious situations and an alternative when medical equipment and volatile agents are unavailable.

References

1. Donchin Y, et al: Military medicine: trauma anesthesia and critical care on the battlefield. Crit Care Clin 1990; 6: 185-202.

2. Bacic A, Gluncic I, Buklijas J: Titrated total intravenous anaesthesia /TNA) in war. J R Army Med Corps 1996; 142: 103-5.

3. Collins SJ, Robinson AL, Holland HF: A comparison between total intravenous anaesthesia using a propofol/alfentanil mixture and an inhalational technique for laparoscopic gynaecological sterilization. Eur J Anaesthesiol 1996; 13: 33-7.

4. Roekaerts PMHJ, Gerrits HJ, Timmerman BE, De Lange S: Continuous infusion of alfentanil and propofol for coronary artery surgery. J Cardiothorac Vasc Anesth 1995: 9: 362-7.

5. Phillips AS, Mirakhur RfC, Glen JB, Hunter SC: Total intravenous anaesthesia with propofol or inhalational anaesthesia with isoflurane for major abdominal surgery. Anaesthesia 1996: 51: 1055-9.

6. Heath Ii,J, Sadler P, Winn JH, McFadzean WA: Nitrous oxide reduces the cost of intravenous anaesthesia. Eur J Anaesthesiol 1996; 13: 369-72.

7. Wilson RJT, Ridley SA: The use of propofol and alfentanil by infusion in military anaesthesia. Anaesthesia 1992; 47: 231-3.

8. Aldrete JA, Kroulik D: A postanesthesic recovery score. Anesth Analg 1970; 49: 924-33.

9. Lenz G. Stehle R: Anesthesia under field conditions: a review of 945 cases. Acta Anaesthesiol Scared 1984; 28: 351-6.

10. Restall J, Tully AM. Ward PJ, Kidd AG: Total intravenous anaesthesia for military surgery: a technique using ketamine, midazolam and vecuronium. Anaesthesia 1988; 43: 46-9.

11. Escarment J, Andreu JM, Herve R. Le Dantec P, Cantais E. Robert P, Quinot JF: Association propofol-ketamine-vecuronium: pour l'anesthesie totalement intraveineuse en situation difficile. Cah Anesthesiol 1996; 44: 447-50.

12. Vuyk J, Mertens MJ, Olofsen E, BurmAGL, Bovill JG: Propofol anesthesia and rational opioid selection. Anesthesiology 1997; 87: 1549-62.

13. Bennett SN, McNeil MM, Bland LA, et al: Postoperative infections traced to contamination of intravenous anesthetic propofol. N Engl J Med 1995; 333: 147-54.

Guarantor: Jean-Marie Saissy, MD Contributors: Laurent Bargues, MD*; Frederique Servin, MDt; Jean-Pierre Ducourau, MD*; Jean-Marie Saissy, MD*

*Hopital d'Instruction des Armees Begin, Service Anesthesie-Reanimation, 69 Avenue de Paris, 94140 Saint-Mande, France.

+Centre Hospitalier Universitaire Bichat, Departement Anesthesie-Reanimation, 46 Rue Henri Huchard, 75018 Paris, France.

This manuscript was received for review in April 1999. The revised manuscript was accepted for publication in September 1999.

Reprint & Copyright by Association of Military Surgeons of U.S., 2000.

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