ADRENALINE INFILTRATION IN VAGINAL SURGERY A Statistical Analysis of the Effect on Operative Blood Loss during Methoxyflurane Anaesthesia

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1 Brit. J. Anaesth. (1969), 41, 609 ADRENALINE INFILTRATION IN VAGINAL SURGERY A Statistical Analysis of the Effect on Operative Blood Loss during Methoxyflurane Anaesthesia BY H. G. SCHROEDER AND J. M. EVANS SUMMARY Blood loss measurements were carried out on 89 cases of vaginal repair and 86 cases of vaginal hysterectomy using a haemoglobin extraction dilution technique. Anaesthesia consisted of thiopentone, methoxyflurane, and nitrous oxide with oxygen. The effects on blood loss of infiltrations of solution 1 in 120,000 and 1 in 240,000 were compared with loss when infiltration was omitted. Results show that either dilution of reduced blood loss significantly, but also showed that the blood loss without infiltration was rarely copious enough to necessitate blood transfusion. The difference in mean blood loss using 1 in 240,000 infiltration, when compared with 1 in 120,000 infiltration, was not statistically significant. It was found that the operative blood loss was greater in premenopausal patients than in postmenopausal patients. The presence of a raised pre-operative blood pressure did not significantly affect the operative blood loss. The control of operative blood loss is of prime concern to both surgeons and anaesthetists. In vaginal surgery the popular method of reducing blood loss has been local infiltration of a solution containing. It is a well-recorded fact that infiltrated subcutaneously or submucosally leads to increased circulating levels of plasma (Brindle, Gilbert and Millar, 1957), which in turn promotes increased risk of myocardial irritability (Gilbert et al., 1958; Lepeschkin et al., 1960) and occasionally fatal ventricular fibrillation (Rosen and Roe, 1963; Forbes, 1966; McVicar, 1967, personal communication). The degree of cardiac irregularity that can be expected is directly related to the total dose of infiltrated, provided accidental intravascular injection does not occur. Although the local infiltration of produces a virtually bloodless field for the surgeon, it can cause anxiety to the anaesthetist and may subject the patient to some degree of risk. It could therefore be claimed that unless the infiltration of is absolutely essential its use can be questioned. The following study was undertaken to measure the actual blood loss during vaginal surgery and to measure the effect of infiltration in two different dilutions on this operative blood loss. MATERIAL AND METHOD Blood loss was determined in 175 cases of vaginal surgery. These consisted of two groups: Group 1. Patients undergoing vaginal repair consisting of anterior and posterior colporrhaphy and amputation of cervix. Group 2. Patients undergoing vaginal hysterectomy (including anterior and posterior colporrhaphy). The patients in both groups 1 and 2 were further sub-divided into three sections: Sub-group A. infiltrated. Sub-group B. Surgery was preceded by multiple site infiltration with 60 ml of 1 in 240,000 in 1 per cent lignocaine solution. Sub-group C. Surgery was preceded by multiple site infiltration with 60 ml of 1 in 120,000 in 1 per cent lignocaine solution. H. G. SCHROEDER,* F.F.A.R.C.S.; J. M. EvANS,t F.R.C.S., M.R.C.O.G.; Jessop Hospital for Women, Sheffield. Present addresses: * Royal Hospital, Sheffield, t Oldham General Hospitals.

2 610 BRITISH JOURNAL OF ANAESTHESIA The multiple site infiltration technique used was similar to that described by Lazar and Krieger (1959). Method of blood loss estimation. The blood loss in each case was determined using a modification of the colorimetric technique described by Alsop, Emery and Zachary (1963). This method necessitates washing all swabs, gowns, drapes and instruments in a polyethylene bath containing 20 litres ammoniated water (8 ml concentrated ammonia). A sample of washing water is read in an EEL portable colorimeter with a green filter (OGRI) and matched tubes (L204). The colorimetric reading of this solution gives a direct reading in millilitres of blood on a previously calibrated chart, according to the patient's pre-operative haemoglobin level. Using this method it is essential to calibrate the colorimeter at each time of use; this is done by reading a tube of Gibson Harrison standard haemoglobin solution against a distilled water blank. In our case, a constant reading of 65 is evidence that the colorimeter sensitivity is stable. The total blood loss was recorded in each case. Pre-operative and postoperative haemoglobin and haematocrit estimations were determined in every patient. Cardiac rate and rhythm during infiltration with was monitored using an electrocardiographic oscilloscope and automatic pulse counter. Blood pressure was monitored by palpation using a sphygmomanometer. Anaesthetic technique. All cases were premedicated with atropine 0.6 mg and morphine 10 mg given intramuscularly, 1 hour pre-operatively. Anaesthesia was induced with sodium thiopentone 6 mg/kg and the resulting thiopentone apnoea used to manually inflate the patient's lungs with a mixture of nitrous oxide (6 l./min) and oxygen (3 l./min) containing 1 per cent methoxyflurane vaporized in a Pentec. After 5-10 inflations, the methoxyflurane concentration was increased to 1.5 per cent and manual inflation by facepiece continued for 10 minutes by the clock. endotracheal tube was used. After 10 minutes of inflation, the patient was allowed to regain spontaneous respiration and was transferred into the operating theatre. Methoxyflurane was continued at 1.5 per cent for 15 minutes, then reduced to 1 per cent. The percentage was increased to 1.5 for 5 minutes before commencing the posterior colporrhaphy. After the posterior repair was commenced, the methoxyflurane was discontinued. This was usually minutes before the estimated end of surgery. Blood pressure remained stable throughout anaesthesia and patients were awake within 5 minutes of completion of surgery. During the initial manual inflation of the patient, hyperventilation was practised in order to retain control of respiration. At no stage was it ever difficult to regain control of ventilation if this became necessary while the patient was breathing methoxyflurane spontaneously. It was sometimes necessary to do this during vaginal hysterectomy on request from the surgeon. Group distribution. Group 1 included 89 cases of vaginal repair. Of these, 32 cases fell into sub-group A, 31 into sub-group B and 26 into sub-group C. The ages of the women in group 1 ranged from 29 years to 74 years, with the average in each sub-group being 56.6, 49.0 and 50.8 years respectively. Group 2 consisted of 86 cases of vaginal hysterectomy, there being 27 cases in sub-group A, 28 in sub-group B and 31 in sub-group C. The ages of the women in group 2 ranged from 34 years to 83 years, the average in each sub-group being 51.6, 50.5 and 50.2 years respectively. RESULTS The results of blood loss measured during operation (table I) show that for vaginal repair in cases receiving no the mean blood loss was 135 ml (SD 75). When in 1 in 240,000 concentration was infiltrated, the mean blood loss was 74 ml (SD 50), a reduction of 45 per cent. However, when the concentration of infiltrated was increased to 1 in 120,000 the mean blood loss was 55 ml (SD 35), a reduction of 59 per cent. The results for vaginal hysterectomy showed a mean blood loss without infiltration of 253 ml (SD 68), with 1 in 240,000 of 131 ml (SD 61), a reduction of 48 per cent, and with 1 in 120,000 a mean blood loss of 119 ml (SD 54), a reduction of 53 per cent.

3 ADRENALINE INFILTRATION IN VAGINAL SURGERY 611 repair 89 cases hysterectomy 86 cases 135 (75) 32 cases 253 (68) 27 cases TABLE I Influence of varying dilutions of infiltrated solution, on mean blood loss (ml) during major vaginal surgery. 1 in 240,000 1 in 120,000 Operation SD in brackets. 74 (50) 31 cases 131 (61) 28 cases 55 (35) 26 cases 119 (54) 31 cases repair 89 cases hysterectomy 86 cases TABLE II Influence of menopause on mean blood loss (ml) in major vaginal surgery cases 272 (51) 17 cases Premenopausal 117 (30) 10 cases 200 (49) 81 (25) 6 cases 135 (34) 18 cases SD in brackets cases 207 (60) 10 cases Postmenopausal 62 (45) 21 cases 99 (48) 16 cases 52 (30) 20 cases 77 (50) 13 cases Influence of infiltration. Statistical analysis of the results by the "f" test and Student t test show that both vaginal repair and vaginal hysterectomy blood losses were significantly reduced by both dilutions of (P<0.0005). The difference in mean blood loss following the use of 1 in 240,000 and 1 in 120,000 was not statistically significant (P>0.05). The mean blood loss associated with the infiltration of is approximately one-half the loss occurring without infiltration, for both operations. Influence of menopause. When the patients are divided into pre- and postmenopausal groups (table II) the significance of the reduction in blood loss with both dilutions of is maintained (P<0.0005). The difference in mean loss between the use of 1 in 240,000 compared with 1 in 120,000 continues to be non-significant (P>0.1), except in the case of vaginal hysterectomy in the premenopausal group, where the difference is highly significant (P<0.0005). In the premenopausal group mean blood losses were significantly greater (P<0.0005) than in the postmenopausal group, with or without infiltration, for both types of operation. This confirms the findings of Johnson and Roddick (1956) and Pratt and associates (1961). Influence of pre-operative hypertension. When the results are subdivided according to the patient's pre-operative blood pressure, assuming a diastolic blood pressure of 90 mm Hg or greater to indicate the presence of hypertension (table IS), the results show conclusive evidence that the mean blood loss did not vary significantly (P>0.5) with the initial blood pressure level, whether was infiltrated or not. The statistically significant difference between "no " and both dilutions of was

4 612 BRITISH JOURNAL OF ANAESTHESIA repair 89 cases hysterectomy 86 cases TABLE III Influence of systemic hypertension on mean operative blood loss during major vaginal surgery. 117 (56) 20 cases 269 (38) 17 cases Diastolic blood pressure above 90 mm Hg 56 (63) 19 cases cases 57 (42) 14 cases 108 (48) 15 cases 137 (60) 245 (50) 10 cases Blood loss mean values (ml) and SD in brackets. Diastolic blood pressure below 90 mm Hg 88 (38) 134 (38) 13 cases 53 (54) cases maintained. The difference between the use of the two dilutions remained statistically nonsignificant. Changes in cardiac rhythm. Throughout the series, when was infiltrated, all patients were observed and monitored for cardiac irregularities. During the infiltration of 1 in 120,000, the response in 89 per cent of cases was an increasing tachycardia following infiltration and, following the peak of tachycardia, the onset of cardiac irregularity of varying severity. Bursts of extrasystoles, multifocal ventricular tachycardia and occasional bursts of nodal rhythm were observed and these persisted until the pulse rate returned to within normal limits. The tachycardia following 1 in 120,000 infiltration commenced in the first 30 seconds, reached a peak at 1^-2 minutes, and then gradually wore off over the next 5-8 minutes. The commonest irregularities observed were atrial and ventricular extrasystoles. Twenty-eight per cent of cases demonstrating cardiac irregularities showed runs of ventricular tachycardia, lasting 5-10 seconds, with reversion to extrasystoles and subsequently to normal rhythm. True nodal rhythm was seen in 5 per cent of these cases but was only of a transient nature. It is possible that the use of 1 per cent lignocaine as a carrying solution for, may have a protective effect because of its cardiac dysrhythmic properties. During the infiltration of 1 in 240,000, tachycardia was far less common, and noticeable cardiac irregularity occurred only in 16 per cent of cases. Levy (1968, personal communication), using a similar quantity of 1 in 400,000 solution of claims that there are no noticeable cardiac irregularities during infiltration even during halothane anaesthesia. DISCUSSION Measurement of accurate blood loss in major vaginal surgery presents problems, due to the fact that a large proportion of blood loss is not retrieved on swabs but trickles into drapes and down through the weighted speculum into the receiving tray. A gravimetric method is therefore prone to inaccuracy, as only the blood loss on swabs is amenable to weighing. It is difficult to weigh gowns, trays and instruments, etc., before they are contaminated. Wexler (1959) partially answered this problem by describing a perineal plastic bag, sewn on to the drapes, into which the speculum was allowed to hang. This served the purpose of catching the trickling blood which was measured postoperatively, and added to the blood loss measured by the gravimetric method. A colorimetric method answers this problem, as all swabs, instruments, drapes and, if necessary, gowns and boots can be washed, so that the final washing fluid contains all the external blood lost by the patient. Both gravimetric and colorimetric methods for measuring blood loss assume a constant haemoglobin level in the patient during the period of measurement. The "educated guess" at blood loss is known to be inaccurate in all types of surgery but notoriously so in vaginal surgery. The adoption of routine operative blood loss measurements, by

5 ADRENALINE INFILTRATION IN VAGINAL SURGERY 613 any method, therefore allows the anaesthetist and surgeon a sense of security in the management of vaginal operations. The results obtained in this series indicate that the total blood loss in uncomplicated surgery for vaginal repair and vaginal hysterectomy, with or without infiltration with the anaesthetic technique described, rarely exceeds 10 per cent of the blood volume. Even if the correction factor of 25 per cent, as suggested by Thornton and associates (1963) and Caceres and Whittembury (1959), is added to allow for "concealed haemorrhage" the average blood loss measured in this series did not exceed 10 per cent of the blood volume and therefore did not necessitate replacement by transfusion. Lazar, Ottway and Offen (1957) stated that haemorrhage was a normal complication of vaginal surgery and that blood transfusions were the rule rather than the exception. They reported that 34 per cent of infiltrated cases required transfusion and 80 per cent of non-infiltrated cases. The authors have not found this to be so; on the contrary, we would state that blood transfusion for vaginal surgery, in our experience, is a rare occurrence. In the last year, 102 vaginal hysterectomies and 275 vaginal repairs have been carried out and in only 2 cases has blood transfusion been necessary. This would confirm the statement of Birkhan (1968). If the results reported here are compared with published results originating from the United States, blood losses far in excess of those measured in our series are recorded and, of course, would therefore necessitate more frequent blood transfusion. The published results (Buchman, 1953; Lazar, Ottway and Offen, 1957; Wexler, 1959; Pratt et al., 1961; Lazar and Snider, 1966) offer no ready explanation for the higher blood losses; the technique of surgery is similar and anaesthetic technique is not mentioned. Duration of surgery may suggest an explanation. Operating time in the present series was for vaginal repair 40 minutes (30-60 minutes) and for vaginal hysterectomy, 105 minutes ( minutes). From evidence available it would appear that in America operating times are generally much longer, vaginal repair 120 minutes ( minutes) and vaginal hysterectomy 180 minutes ( minutes). These times were stated by Patrick (1968, personal communication) during an extensive tour of the United States. All the American observers used the gravimetric method to estimate blood loss, which would tend to underestimate the total blood loss. The British observers, Loudon and Scott (1960) used a gravimetric method and obtained results approaching those found by the writers. Moir (1968) used colorimetry and obtained, in patients breathing halothane, blood loss results that were slightly higher. This would suggest that when respiration is spontaneous, blood loss is less when methoxyfiurane is inhaled than when halothane is used for anaesthesia. In this series multiple site infiltration, using 1 in 120,000, reduced the operative blood loss by an average of 55 per cent. This compares with the 60 per cent reduction reported by Lazar and Krieger (1959). However, multiple site infiltration with in half this concentration led to a reduction in the operative blood loss of an average of 45 per cent. Statistical analysis of this difference proves it to be nonsignificant. Therefore, when it is a fact that the myocardial arrhythmias produced by are directly proportional to the total dose injected, it appears to be unnecessary to infiltrate in a concentration of 1 in 120,000 if similar results can be achieved with 1 in 240,000. An eveir safer precaution would be to abandon the use of. entirely. Gynaecologists have drawn attention to two' factors associated with bleeding during vaginal surgery. The first is the difficulty of making an accurate assessment of the loss. This is readily answered by the use of any colorimetric technique, such as the one used in this series (Alsop, Emery and Zachary, 1963) or the Medatron discussed by Thornton and associates (1963). The second factor is the interference with the operative vision brought about by the almost constant oozing. Accurate plastic surgery demands a blood-free field. Blood loss from veins and arteries can be readily controlled by ligatures and clamps, but the constant capillary oozing has been accused of obliterating the surgeon's view of the operative field. Multiple site infiltration of a solution containing satisfies both these factors, but does so at some risk to the patient. Therefore, if used at all, it should be used in the lowest

6 614 BRITISH JOURNAL OF ANAESTHESIA possible dilution compatible with the provision of the blood-free field required. ACKNOWLEDGEMENT We would like to thank Mr. A. K. Richards and Mr. D. R. Taylor of the Department of Probability and Statistics, University of Sheffield, for their help with the statistical analysis of the results. REFERENCES Alsop, W., Emery, J. K., and Zachary, R. B. (1963). Measurement of blood loss during operation. Brit, med. J., 1, 125. Birkhan, J. (1968). Blood loss during major vaginal surgery (Correspondence). Brit. J. Anaesth., 40, 916. Brindle, G. F., Gilbert, R. G. B., and Millar, R. A. (1957). The use of Fluothane for neurosurgery a preliminary report. Canad. Anaesth. Soc. J., 4, 265. Buchman, M. I. (1953). Blood loss during gynecological operations. Atner. J. Obstet. Gynec, 65, 53. Caceres, E., and Whittembury, G. (1959). Evaluation of blood loss during surgical operations. Surgery, 45, 681. Forbes, A. M. (1966). Halothane, and cardiac arrest. Anaesthesia, 21, 22. Gilbert, J. L., Lange, G., Polevoy, I., and McBrook, S. C. (1958). Effects of vasoconstrictor agents on cardiac irritability. 7. Pharmacol, exp. Ther., 123, 9. Johnson, B., and Roddick, J. W. (1956). Blood loss in vaginal surgery. Obstet. and Gynec., 7, 704. Lazar, M. R., and Krieger, H. A. (1959). Blood loss in vaginal surgery a comparative study. Obstet. Gynec, 13, 707. Ottway, J. P., and Offen, J. A. (1957). Controlled blood loss in vaginal surgery. Obstet. Gynec, 10, 198. Snider, E. A. (1966). New hemostatic agent for geriatric gynecology. Obstet. Gynec, 27, 341. Lepeschkin, E., Marchet, H., Schroeder, G., Wagner, R., depaula, C, SUva, P., and Raab, W. (1960). Effects of epinephrine and norepinephrine on the E.C.G. of 100 normal subjects. Atner. J. Cardiol., 5, 594. Loudon, J. D. O., and Scott, D. B. (1960). Blood loss in gynaecological operations. J. Obstet. Gynaec. Brit. Emp., 67, 561. Moir, D. D. (1968). Blood loss during major vaginal surgery: a statistical study of the influence of general anaesthesia and epidural anaesthesia. Brit. J. Anaesth., 40, 233. Pratt, J. H., Nelson, G. A., Wilcox, C. F. (m), and Bjercke, L. T. H. (1961). Blood loss during vaginal hysterectomy. Obstet. Gynec, 15, 101. Rosen, M., and Roe, R. B. (1963). Adrenaline infiltration during halothane anaesthesia: a report of two cases of cardiac arrest. Brit. J. Anaesth., 35, 51. Thornton, J. A., Saynor, R., Schroeder, H. G., Taylor, D. G., and Verel, D. (1963). Estimation of blood loss with particular reference to cardiac surgery. Brit. J. Anaesth., 35, 91. Wexler, D. J. (1959). Measurement of blood loss in vaginal surgery. Obstet Gynec, 13, 213. INFILTRATION D'ADRENALINE DANS LA CHIRURGIE VAGINALE. UNE ETUDE STATISTIQUE DE L'EFFET SUR LA PERTE SANGUINE PEROPERATOIRE AU COURS DE L'ANESTHESIE AU METHOXYFLURANE SOMMAIRE Les pertes sanguines ont ete mesurees a l'aide d'une technique d'extraction-dilution d'hemoglobine, au cours de 89 reparations vaginales et 86 hysterectomies par voie vaginale. L'anesthesie se fit au moyen de thiopentone, methoxyflurane et protoxyde d'azote avec oxygene. L'influence sur la perte sanguine d'infiltrations d' 1: et 1: a ete comparee avec les pertes en absence d'infiltrations d'. Les resultats prouvent que les deux concentrations d' reduisent significativement la perte de sang mais montrent egalement que les pertes en absence d'infiltrations d' ne sont que rarement si abondantes, qu'elles necessitent une transfusion de sang. La difference entre la quantite moyenne de sang perdu sous infiltration d' 1: et celle sous la concentration de 1: n'est pas statistiquement significative. II a ete constate que les pertes sanguines sont plus importances chez les patients en premenopause que chez les femmes menopausees. L'existence pre'operatoire d'une hypertension n'influence pas significativement la quantite de sang perdu pendant l'operation. INFILTRATION MIT ADRENALIN BEI VAGINALOPERATIONEN: EINE STATIS- TISCHE ANALYSE DER WIRKUNG AUF DEN OPERATIVEN BLUTVERLUST UNTER METHOXYFLURAN-NARKOSE ZUSAMMENFASSUNG In 89 Fallen von reparationen und 86 Fallen von vaginaler Hysterektomie wurden mit Hilfe eines Harnoglobin-Extraktions-Verdiinnungs-Testes der Blutverlust gemessen. Als Narkosemittel wurden Thiopenton, Methoxyfluran sowie Lachgas mit Sauerstoff verwendet. Die Effekte einer Adrenalin-Infiltration in Konzentrationen von 1: und 1: auf den Blutverlust wurden mit dem Blutverlust ohne Adrenalin-Infiltration vergleichen. Es zeigte sich, dafi mit jeder der beiden Adrenalin-Konzentrationen der Blutverlust wesentlich herabgesetzt werden konnte; ohne Infiltration war der Blutverlust jedoch nur selten so stark, dafl eine Transfusion erforderlich wurde. Der Unterschied des durchschnittlichen Blutverlustes nach der Adrenalin-Konzentrarion von 1: gegeniiber der von 1: war statistisch nicht signifikant. Es wurde festgestellt, dafi der operative Blutverlust der Patientinnen vor der Menopause grofler war als nach derselben. Eine yor der Operation vorhandene Hypertonie hatte keinen wesentlichen EinfluB auf den operativen Blutverlust.

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