Injection of morphine loco dolenti recommended as early as 1876.

The peripheral site of action of opioids was proved some 20 years ago. The concept of the peripheral action of morphine, however, appears to be over 100 years older. We report on the contents of a paper, presented on 28 April 1876 at the meeting of the Finnish Medical Association ("Finska Läkarsällskapet"), on the use of morphine and its sites of action. The author was Professor Knut Felix von Willebrand, whose details are included. Prof. v. Willebrand starts by focusing on several unwanted side effects, often seen in connection with morphine administration, and advises how they can be avoided by using the pupils of the eye as a manometer for tolerance of morphine, as suggested by Vibert. After having presented four case reports which illustrate the use of morphine in his own practice, Prof. v. Willebrand explains his conception of the sites of action of morphine. The paper gives a lively picture of the use of morphine about 125 years ago. Furthermore, it indicates that Prof. v. Willebrand believed firmly in the peripheral site of action of morphine and recommended to inject morphine loco dolenti whenever possible.

Finland's first anaesthesia revealed by newspapers.

BACKGROUND: According to the literature on the history of anaesthesia, Finland's first anaesthesia was given on March 8, 1847 for a ligature of an aneurysm of the subclavian artery. It has, however, not been possible to verify the date with certainty. We therefore wanted to find out whether newspapers might give additional information and how this exceptionally important medical invention had been received by the Finnish newspapers. METHODS: Microfilms of the 10 newspapers which appeared in Finland in 1847 were studied at the Helsinki University library. RESULTS: The first report which made reference to English newspapers was published on February 10 by "Borgå Tidning". On March 6, "Helsingfors Tidningar" wrote that two anaesthesias had already been given in Helsinki; the first of them for a difficult varicose veins operation and the second for an exarticulation of a shoulder. But there was no information regarding the dates of the operations. Fortunately, both operations had been recorded in the patient diary of the clinic, although without any information about the anaesthesia. According to the diary, Johan August Orn was operated for varicose veins on February 16 and Anders Gustaf Henrikson had his right arm exarticulated on March 3. Both patients recovered. In total, only six pieces of news on anaesthesia were found. CONCLUSIONS: Finland's first anaesthesia was given on February 16, 1847, which is three weeks earlier than had been previously assumed.

A survey of the ASA physical status classification: significant variation in allocation among Finnish anaesthesiologists.

BACKGROUND: The American Society of Anesthesiologists' (ASA) Classification of Physical Health is a widely used grading system for preoperative health of the surgical patient. In previous studies conducted in North America and Great Britain, considerable variation in the ASA classification allocation has been reported. We hypothesised that in smaller and culturally more homogeneous countries there might be less variation in the ASA classification. METHODS: A postal questionnaire depicting 10 hypothetical patient cases was sent to 249 randomly selected members of the Finnish Society of Anaesthesiologists. Responses of anaesthesiologists working in university teaching and non-teaching hospitals were compared, as well as the answers of specialists and non-specialists. RESULTS: Responses were received from 108 anaesthesiologists (response rate 43%). There was marked variation in the classification of all the 10 cases: 1 case was classified to all five possible grades (ASA grades I-V). In 2 cases, there was significant variation between anaesthesiologists working in university teaching and non-teaching hospitals. There was no difference in the grading between specialist and non-specialist anaesthesiologists. CONCLUSION: In a small and culturally homogeneous country, like Finland, there exists similar wide variation in the ASA classification as has been previously reported from larger and culturally more heterogeneous countries. The significant variation should always be considered when using this classification in clinical or scientific work.

Quantitation of the enflurane-sparing effect of alfentanil during general surgery.

The authors quantitated the enflurane-sparing effect of alfentanil during N2O/O2 anaesthesia in 50 patients undergoing body surface surgery and in 50 patients undergoing upper abdominal surgery. Patients were assigned to one of five treatment regimens (10 patients each group, double-blind administration) as follows: placebo bolus followed by placebo infusion (group I); or alfentanil bolus (30 micrograms kg-1) followed by infusion of placebo (group II) or alfentanil, at the rate of 10 (group III), 20 (group IV), or 40 (group V) micrograms kg-1 h-1. Anaesthesia was induced with thiopentone and vecuronium, and neuromuscular block was kept at 85-90% by continuous infusion of vecuronium. Increases in spontaneous electromyographic activity of neck muscles (NEMG) and in systolic blood pressure (SBP) served as criteria of inadequate anaesthesia. When such increases occurred, enflurane was given in 0.2% steps (end-tidal concentration) of 5 min each, until the increases were suppressed. The relationship between increases in NEMG and increases in SBP was inconsistent: only 10% of the increases occurred simultaneously. With alfentanil, the consumption of enflurane decreased by as much as 70% (P < 0.001) during superficial surgery and 50% (P < 0.05) during abdominal surgery.

Dependence of the adequacy of muscle relaxation on the degree of neuromuscular block and depth of enflurane anesthesia during abdominal surgery.

We studied the intensity of neuromuscular block that is adequate for surgical relaxation at different end-tidal levels of enflurane during N2O-O2-fentanyl anesthesia in 30 patients undergoing upper abdominal surgery. After induction of anesthesia with thiopental 4-6 mg/kg and vecuronium 0.07 mg/kg intravenously (i.v.), patients were randomly assigned to receive nitrous oxide-oxygen (2:1) and enflurane at 0.3% (Group I), 0.6% (Group II), or 1.2% (Group III) end-tidal level throughout anesthesia. The initial neuromuscular block was allowed to terminate and additional increments of 1 mg vecuronium were given when indicated by clinical signs or by spontaneous electromyography of neck muscles. In Group I additional vecuronium had to be given 62 times and in Groups II and III, 33, and 16 times, respectively. The mean (SD) neuromuscular block at the time of additional vecuronium was 75.9% +/- 20.7%, 62.5% +/- 20.1%, and 39.3% +/- 21.1% in Groups I to III, respectively. We conclude that there was a clear linear relationship between the end-tidal concentration of enflurane and the degree of neuromuscular block necessary to produce adequate surgical muscle relaxation (P < 0.001).

Assessment of the interaction between atracurium and suxamethonium at 50% neuromuscular block using closed-loop feedback control of infusion of atracurium.

We have studied the effect of prior administration of suxamethonium on the infusion requirements of atracurium at 50% neuromuscular block in patients undergoing elective general surgery. Anaesthesia was maintained with nitrous oxide in oxygen, propofol and fentanyl. Of 20 patients given atracurium, only 10 were given prior administration of suxamethonium 1 mg kg-1. At the beginning of the infusion, atracurium 0.3 mg kg-1 was given by bolus administration. Interaction between the two drugs was assessed by determining the steady state rate of infusion necessary to produce a constant 50% neuromuscular block. This was accomplished by applying non-linear curve fitting to data on the cumulative dose requirements during anaesthesia. The neuromuscular blocking effect was found to be similar with or without prior administration of suxamethonium. The mean steady-state rate of infusion for atracurium was 0.19 (SD 0.03) mg kg-1 h-1 for patients given suxamethonium and 0.18 (0.09) mg kg-1 h-1 for those who were not given suxamethonium. Thus prior administration of suxamethonium did not affect the infusion requirements of atracurium at 50% neuromuscular block, unlike the situation at constant 90% neuromuscular block.

Quantifying the interaction of rocuronium (Org 9426) with etomidate, fentanyl, midazolam, propofol, thiopental, and isoflurane using closed-loop feedback control of rocuronium infusion.

The present study was designed to evaluate the interactions of rocuronium with etomidate, fentanyl, midazolam, propofol, thiopental, and isoflurane using closed-loop feedback control of infusion of rocuronium. Sixty patients were randomly assigned to one of six sequences where anesthesia was maintained with etomidate, fentanyl, midazolam, propofol, or thiopental and nitrous oxide, or with isoflurane and nitrous oxide. The possible interaction of rocuronium with the anesthetics was quantified by determining the asymptotic steady-state rate of infusion (Iss) of rocuronium necessary to produce a constant 90% neuromuscular block. This was accomplished by applying nonlinear curve fitting to data on the cumulative dose requirement during the initial 90-min period after bolus administration of rocuronium. Patient characteristics and controller performance, i.e., the ability of the controller to maintain the neuromuscular block constant at the set-point, did not differ significantly between the groups. Iss values calculated per lean body mass were 0.64 +/- 0.22, 0.60 +/- 0.15, 0.61 +/- 0.21, 0.67 +/- 0.31, 0.63 +/- 0.15, and 0.39 +/- 0.17 mg.kg-1.h-1 in the etomidate, fentanyl, midazolam, propofol, thiopental, and isoflurane groups, respectively. The isoflurane group had a lower steady-state rate of infusion of rocuronium than the other five groups (P < 0.05). Compared to intravenous anesthetics, etomidate, fentanyl, midazolam, propofol, or thiopental, isoflurane reduced the infusion requirement of rocuronium by 35%-40%.

Quantitation of the interaction of rocuronium bromide with etomidate, fentanyl, midazolam, propofol, thiopentone, and isoflurane using closed-loop feedback control of infusion of rocuronium.

Sixty patients were randomly assigned to one of six groups (n = 10 in each case) in which anaesthesia was induced and maintained with etomidate, fentanyl, midazolam, propofol or with thiopentone and N2O, or isoflurane and N2O. After obtaining control measurements, rocuronium 0.6 mg kg-1 was given for intubation followed by an infusion, controlled by closed-loop feedback at 90% block. The steady-state rates of infusion were (in the same order) 0.64 +/- 0.22, 0.60 +/- 0.15, 0.61 +/- 0.21, 0.67 +/- 0.31, 0.63 +/- 0.15 and 0.39 +/- 0.17 mg kg-1 h-1 (Mean +/- SD). The intravenous agents did not interact with recuronium to any clinically significant degree. Isoflurane reduced the requirements by 35-40%.

Intravenous morphine and oxycodone for pain after abdominal surgery.

Intravenous morphine and oxycodone were given double blind in doses of 0.05 mg/kg after major abdominal surgery to 39 patients. The dosing interval was 5 min, until the patient did not want any further analgesics. Less oxycodone was needed than morphine, both to achieve the "first state of pain relief" (13.2 mg vs. 24.9 mg) and during the whole 2-h study period (21.8 mg vs. 34.2 mg). The "first state of pain relief" was achieved faster (28 min vs. 46 min) and lasted longer (39 min vs. 27 min) with oxycodone than morphine. Morphine caused more sedation and a greater decrease in the mean arterial blood pressure than oxycodone. In other respects the two opioids were comparable.

The efficacy of intravenous indomethacin in prevention of postoperative pain.

Since intravenous prophylactic anti-inflammatory agents have been suggested to reduce or even replace opiates in postoperative pain therapy, we studied the demand for morphine in 45 patients recovering from abdominal surgery who had received a baseline infusion of either indomethacin, morphine or saline placebo. When extubated after inhalational anaesthesia, each patient received an i.v. bolus of either 0.5 mg.kg-1 indomethacin, 0.07 mg.kg-1 morphine or saline placebo. Thereafter a 20-h infusion of the same test analgesic was started, either 0.1 mg.kg-1.h-1 indomethacin, 0.03 mg.kg-1.h-1 morphine or saline placebo. For additional analgesia, a patient-controlled analgesia device (PCA) delivering 5-mg boluses of morphine was used. For the first 5 postoperative hours, significantly more (P less than 0.05) PCA morphine was needed in the indomethacin group (35 mg) than in the morphine group (24 mg), while the placebo group demanded mean 30 mg. For equal analgesia (measured by VAS and VRS) between 5-20 h, similar amounts (mean 23 and 19 mg) of PCA morphine were required in the indomethacin and morphine groups, in contrast to the placebo group (mean 40 mg) (P less than 0.001). Morphine infusion increased the total consumption of morphine by 25% as compared to placebo. We conclude that, following abdominal surgery, the analgesic effect of indomethacin infusion became apparent after the first 5 postoperative hours, thereafter reducing the demand for PCA morphine by about 40%. Continuous morphine infusion diminishes the postoperative demand for PCA morphine, but also increases the total morphine consumption.

Sensitivity, specificity and predictive value of the sensation of warmth as a method of detecting inadvertent subarachnoid injection of local anaesthetic when performing extradural blocks.

In order to test if the rate of onset of sensation of warmth in the legs after the injection of 0.5% bupivacaine might discriminate between subarachnoid and extradural injection, 150 urological patients were allocated randomly to receive either spinal anaesthesia with isobaric (IS) or hyperbaric (HS) 0.5% bupivacaine, or extradural anaesthesia with isobaric 0.5% bupivacaine. The volume of the local anaesthetic for spinal anaesthesia and for the extradural test dose was 3-4 ml. The patients were asked to report at once if they had a sensation of warmth in the legs during or after injection of local anaesthetic. The mean time to the sensation of warmth was significantly shorter in the spinal groups (80 (SEM 10) s in IS and 76 (8.0) s in HS) than in the extradural group (558 (38) s). However, six patients in the IS and two in the HS group had no sensation of warmth.

Spontaneous EMG activity for detection of arousal during general anaesthesia--comparison between recordings from frontal and neck musculature.

Monitoring of the spontaneous electromyographic activity of the frontal muscles (FEMG) is used for detection of impending arousal during general anaesthesia. Since the irritation caused by an endotracheal tube in situ might enhance the sensitivity of neck muscles in detecting arousal, EMG recordings from sternocleidomastoid muscles (NEMG) were compared to FEMG recordings under five different clinical conditions with 10 patients in each group. Two Anesthesia and Brain Activity Monitors (ABM, Datex Instrumentarium, Helsinki) were used simultaneously for recordings. NEMG was more sensitive than FEMG in detecting increases in EMG activity under all five conditions, although less distinct under conditions with a profound (90-100%) neuromuscular blockade. The results thus support our initial hypothesis and favour the use of neck muscles for monitoring. This, however, does not allow simultaneous recording of EEG through the same electrodes.

Assessment of anaesthetic adequacy with upper facial and abdominal wall EMG.

We compared changes in biopotentials arising from upper facial (FEMG) and abdominal (AEMG) muscles associated with alterations in alveolar enflurane concentration and neuromuscular block. Induction of anaesthesia significantly reduced both FEMG and AEMG mean amplitudes (-60% and -43%, respectively). Neuromuscular blocker-induced abolition of the electrically evoked thenar EMG response did not prevent FEMG and/or AEMG activation during endotracheal intubation. Decreasing the alveolar enflurane concentration was associated with an increase in FEMG amplitude prior to visible signs of arousal in half of the patients. Movement and other signs of inadequate anaesthesia were associated with distinct increases in FEMG amplitude in 29 out of 30 patients. Recovery from neuromuscular block during unchanged alveolar enflurane concentration was associated with increasing amplitudes of both FEMG and AEMG. Finally, very low-amplitude FEMG recordings were always associated with relaxed abdominal muscles.

Suxamethonium-induced facilitation of spontaneous frontal EMG activity.

The behaviour of spontaneous frontal electromyographic activity (FEMG) was studied during the recovery from suxamethonium and vecuronium block. In order to obtain comparable conditions in the study groups, the duration of the suxamethonium block was prolonged with a suxamethonium infusion. The FEMG was continuously recorded and the evoked electromyographic (EEMG) and twitch tension (ETT) responses were measured every 10 s from the thenar muscles. The median FEMG remained at the base level in 8 of the 12 vecuronium patients, despite a 50% recovery of EEMG. In the suxamethonium group there was an increase in FEMG in all six patients when EEMG had recovered to 10%, and significantly higher FEMG readings were obtained during further recovery from the block. Thus, early recovery of neuromuscular transmission is detected by FEMG more easily when suxamethonium is used instead of vecuronium. The different behaviour of FEMG may reflect a difference in the recovery ratio of ETT/EEMG or in the anaesthetic depth caused by the two types of neuromuscular blockers.