POSTOPERATIVE ANALGESIA AND LUNG FUNCTION: A COMPARISON OF NARCOTIC ANALGESIC REGIMENS

Brit. J. Anaesth. (1973), 45, 346

POSTOPERATIVE ANALGESIA AND LUNG FUNCTION: A COMPARISON OF NARCOTIC ANALGESIC REGIMENS J. I. ALEXANDER, R. K. PARIKH AND A. A. SPENCE SUMMARY

In narcotic* medication, there is a conflict of interests between the desire to relieve pain and anxiety about the effect of potent analgesic drugs on lung function. This has resulted in a widespread practice of withholding drugs until the patient's pain tolerance is exceeded. This is commonly known as administration "on patient demand". Spence and Smith (1971) noted that patients with upper abdominal wounds on this regimen received an average of only 26 mg morphine in the first 24 hours after surgery and 18 mg on the second day. Our own enquiries indicate that this is typical of practice in most centres. They reported also that these patients had much larger alveolar/arterial oxygen tension differences ((A-a) Poa diff.) than a comparable group managed with continuous extradural nerve block. Since continuous extradural nerve block is not feasible for routine use and because there might be scope for increasing the amount of analgesics given in the postoperative period, it is important to know what effect increased narcotic medication would have on postoperative lung function. In this study, we have measured arterial blood gases before and after operation in groups of patients having a standard upper abdominal operation. We have reported previously a relationship between postoperative changes in blood gases and changes in lung volumes, notably functional residual capacity (FRC) (Alexander et al., 1973). Therefore, FRC has been measured and also the vital capacity (VC). We have compared the effect of the following three methods of narcotic analgesia on these measurements: (1) Given ijn. "on demand". * In this paper, the term "narcotic" is taken to mean a drug "producing sleep as well as analgesia" (Goodman and Gillman, 1965).

(2) Larger amounts (i) given regularly by ijn. injection; (ii) given continuously by i.v. infusion. PATIENTS AND METHODS

Studies were made on 75 healthy male volunteer patients, all with duodenal ulcers, who were admitted for elective vagotomy and drainage operations. Lung volumes and arterial blood gases were measured on the day before operation and on the first, second and fifth days after operation. The patients were randomly allocated to one of four analgesic regimens: A Pentazocine 45 mg ijn. on demand. B Pentazocine 45 mg ijn. 4-hourly for 48 hours. C Pentazocine 540 mg in continuous intravenous infusion over 48 hours. D Morphine 10 mg i.m. on demand. Patients in Groups A, B and C were premedicated with pentazocine 45 mg and atropine 0.6 mg intramuscularly 1 hour before operation. In addition, they were given pentazocine 45 mg intravenously during the operation. In Group D, morphine 10 mg was substituted for pentazocine. In other respects, both the general anaesthesia and the surgical procedure (vagotomy and pyloroplasty or gastroenterostomy through a right paramedian incision) were standard in all four groups. During their stay in the recovery room, a period ranging from 1 to 6 hours, the patients breathed 35-40% oxygen in nitrogen. In all cases, intravenous infusions were started before incision and were continued for 48 hours postoperatively. If pentazocine was given in an infusion, it was started immediately after the operation. J. I. ALEXANDER, M.B.,B.S., F.F.A.R.CS.; R. K. PARIKH, M.B.3.S., F.F.AJLC.S.; A. A. SPENCE, M.B.,CH.B., F.F.AJLCS.;

University Department of Anaesthesia (Western Infirmary), 4 Lilybank Gardens, Glasgow G12 8RZ.

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Eighty-eight men who underwent elective vagotomy and drainage were allocated to one of two methods of postoperative narcotic analgesia. Either the analgesia was given intramuscularly when requested or it was given regularly by intramuscular injection or continuous intravenous infusion. Although there was a considerable difference in total quantities of drug given by these two methods, there were only marginal differences of pulmonary gas exchange or lung volumes.

POSTOPERATIVE ANALGESIA AND LUNG FUNCTION

347

TABLE I. Number, ages, heights, weights and tobacco consumption of patients studied in each analgesic regimen. Tobacco Mean Mean Mean consumption age height weight (cigarettes/ Group Analgesic regimen Number (yr) (cm) (kg) day*)

In the other regimens, the first dose of analgesic drug was given when the patient first complained of pain. Those in charge of treatment were free to alter the analgesic regimen and remove the patient from the study if they so wished. This was done in the case of 5 patients whose results are not included. Lung junction studies. The vital capacity and its subdivisions were measured by means of a Vitalograph Spirotest I spirometer. The functional residual capacity was measured by the closed-circuit nitrogen dilution technique (Herrald and McMichael, 1939) using the Godart Nitrograph to measure the concentration of nitrogen in the circuit. The arterial blood gases were measured from a radial artery sample taken into a heparinized syringe under anaerobic conditions. The oxygen and carbon dioxide tensions, and pH, were measured immediately, using the appropriate Radiometer electrodes. The patient breathed room air prior to and during the sampling of arterial blood. All volumes were corrected to BTPS and, where appropriate, the gas tensions were corrected for any difference in temperature between the electrode and the patient, using the Severinghaus slide rule (Severinghaus, 1966). A correction of 1.065 was applied to the arterial Po, because the Po2 electrode was calibrated with air. This factor had been determined previously with tonometered whole blood. The functional residual capacity values were corrected for the nitrogen which had been washed out from the tissues during the time of measurement (Lundin, 1953). (A-a)Po, diff was calculated as follows: (A-a)Po2 diff=[Pi O l -(Pa c o ,/R)]-Pa O j

41.3

173.2

±2.7

±1.5

68.8

±2.0

183

±2.3

39.1

170.2

68.6

15.7

±2.5

±2.0

±2.4

±2.4

42.8

170.2

66.3

12.6

±2.5

±1.5

±1.8

±2.4

42.1

172.7

±3.2

±1.5

663 13.9 • ±3.0 ±3.3 the equivalent of standard sized cigarettes

The respiratory quotient (R) is assumed to be constant and to have the value 0.8 (Ellison et aL, 1966). Additional study. After completion of the study, an additional 13 patients having had the same type of surgery were given morphine 10 mg by intramuscular injection 4-hourly for 48 hours. Their treatment and measurements were identical to those for the other patients except that their allocation to the analgesic regimen was not random. RESULTS

Details of the patients studied in each analgesic regimen are shown in table I. There are no significant inter-group differences in the ages, heights or weights, and no important difference in tobacco consumption. Table II shows the average amount of analgesic received by each group of patients. Although patients in Groups B and C should have received 540 mg of pentazocine over 48 hours, human error and the TABLE II. Amount of analgesic drug given in first 48 hours after vagotomy and drainage (±SEM).

Group

Analgesic regimen

A

Pentazocine 45 mg i.m. as requested

B

Pentazocine 45 mg Lm. 4-hourly for 48 hours

C

Pentazocine in continuous Lv. infusion for 48 hours

D

Morphine 10 mg ion. as requested

Amount given in 24 hours (mg) 137.7

±13.5 222.5 ±12.9 274.0

±3.0 27.4

±2.3

Amount given in 48 hours (mg) 202.0

±23.7 436.1 ±28.0 521.0 ±10.1 46.7 ±3.4

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19 Pentazocine 45 mg i.m. as requested B Pentazocine 45 mg Lm. 19 4-hourly for 48 hours C Pentazocine in continuous 18 i.v. infusion for 48 hours D Morphine 10 mg ijn. 19 as requested * Where tobacco is consumed in some other form, is given A

BRITISH JOURNAL OF ANAESTHESIA

348 vagaries of intravenous infusions were responsible for small variations. In Groups A and D, we did not attempt to influence the total amount of drug given by the nurses. The ratio of the means (pentazodne: morphine) was 5:1 for the first 24 hours and 4.3:1 for the first 48 hours. Table E l shows arterial Pco a values before and after operation. There are no significant inter-group differences on any of the days of measurement and no important postoperative changes in any group. Table IV shows arterial Po a values before and after operation. There is a significant difference between III.

Group A B C D

TABLE

Group A B C D

Mean arterial carbon dioxide tension {mm Hg) before and after vagotomy and drainage (±SBM). Postoperative days Preop. 5 1 2 Analgesic regimen day

Fentazocine 46 mg i.m. as requested Pentazocine 45 mg i.m. 4-hourly for 48 hours Pentazocine in continuous i.v. infusion for 48 hours Morphine 10 mg i.m. as requested IV.

36.3

38.0

±1.5 ±0.9

±0.9 36.2 ±0.9

36.5 ±0.8 36.5 ±1.1 34.6 ±0.8

35.9 ±1.1

34.9 ±1.0

36.8 ±0.9

36.5

37.3

37.0

±0.8 35.6 ±0.6 35.8 ±0.8

±1.1

±1.2

36.8

±0.6

37.8

Mean arterial oxygen tensions{mm Hg ) before and after vagotomy and drainage {±SEM). Postoperative days Preop. 1 2 5 day Analgesic regimen

Pentazocine 45 mg i.m. as requested Pentazocine 45 mg i.m. 4-hourly for 48 hours Pentazocine in continuous i.v. infusion for 48 hours Morphine 10 mg i.m. as requested

90.9

73.1

75.6

84.8

±2.1 88.2 ±1.7 84.0 ±2.7

±2.0

±2.4

±2.0 69.5 ±2.4

±2.3

±3.0 84.3 ±2.1 82.6 ±2.4

82.6 ±1.9

66.5 ±2.3

74.0

74.6

70.9

±2.1 62.6

79.3

±2.8

±2.7

TABLE V. Mean alveolar 1arterialoxygen tension differences {mm Hg) before and after vagotomy and drainage {±SEM). Postoperative days

Group

Analgesic regimen

A

Pentazocine 45 mg i.m. 88 requested Pentazocine 45 mg ijn. 4-hourly for 48 hours Pentazocine in continuous i.v. infusion for 48 hours Morphine 10 mg i.m. as requested

B C D

Preop. day

12.9 ±2.4 15.9 ±1.7 19.3 ±1.8

1

2

5

29.7

27.3

17.9

±2.4

±2.8

±3.3

±1.8 32.7 ±2.7

±2.1 32.3 ±2.3

±2.8

30.1

27.4

18.0

22.7

±2.4

19.9

36.6

41.7

24.9

±2.2

±2.5

±2.6

±3-2

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TABLB

the Group D mean of 82.6 mm Hg and the mean values of Group A (90.9 mm Hg; (P<0.05)) and Group B (88.2 mm Hg; (P<0.05)). The Group C mean (84 mm Hg) is significantly different from that of Group A (P<0.05). The mean values in each group fall as a result of operation, returning towards the preoperative value on the second and fifth postoperative days. Table V shows that there are corresponding preoperative inter-group differences in alveolar/arterial oxygen tension difference, the mean values in Groups C and D being higher than those in Group A (P<0.05).

POSTOPERATIVE ANALGESIA AND LUNG FUNCTION

difference on the fifth day. There is a significant difference from the preoperative mean value in Groups A and D (P<0.03 for both groups) but not in Groups B and C Table VII shows the effect of operation on F R C The postoperative FRC is expressed as a percentage of the preoperative value in each patient. FRC falls as a result of operation. The lowest values are on the first postoperative day and there is considerable improvement by the fifth day. The fall in FRC in Group C on the first day is significantly greater th«" that in Group A (P<0.02), but there are no other significant inter-group differences. Table VHI shows

TABLE VI. Increase in alveolar janerial oxygen tension difference {mm Hg) as a result of vagotomy and drainage {±SEM). Postoperative days Group Analagesic regimen A Pentazocine 45 mg i.m. as requested B Pentazocine 45 mg i.m. 4-hourly for 48 hours C Pentazocine in continuous i.v. infusion for 48 hours D Morphine 10 mg Lm. as requested

1

2

5

16.7

14.9

5.5

±2.2 14.1

±2.1

±2.5

11.1

3.1

±2.1

±1.8

±2.5

13.4

11.9

2.3

±2.4

±2.6

±2.6

15.9 ±2.2

20.5 ±2.2

4.5 ±2.2

TABLE VII. The effect of vagotomy and drainage on FRC. The postoperative FRC is expressed as a percentage of the preoperative value (±S.EAf). Postoperative days Group A B C D

Analgesic regimen

Pentazocine 45 mg i.m. as requested Pentazocine 45 mg i.m. 4-hourly for 48 hours Pentazocine in continuous i.v. infusion for 48 hours Morphine 10 mg i.m. as requested

1

75.7 ±2.9 70.2

±3.7 65.4

±3.6 71.6

±3.8

2

79.6

±3.5 77.7

±3.3 78.9

±3.8 75.7 ±3.4

5

89.2

±4.1 95.5 ±3.8 92.1 ±3.7 87.2

±3.2

TABLE VIII. The effect of vagotomy and drainage on VC. The postoperative VC is expressed as a percentage of the preoperative value ( ± SEM). Postoperative days Group A B C D

Analgesic regimen Pentazocine 45 mg Lm. as requested Pentazocine 45 mg i.m. 4-hourly for 48 hours Pentazocine in continuous i.v. infusion for 48 hours Morphine 10 mg i.m. as requested

1

32.7

±2.8 32.5

±2.6 38.6 ±3.3 39.0 ±3.3

2

48.8

±4.2

41.3

±3.0 52.0

±3.5

44.7

±3.2

5

73.6

±5.3 74.6

±3.6 83.4 ±4.3 76.0 ±3.7

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Table VI shows the mean increase in alveolar/ arterial oxygen tension difference on each of the 3 postoperative days compared with preoperative measurement (Measurements discarded for technical reasons account for the small discrepancies between this table and table V.) On the first day after operation, there are no significant inter-group differences. On the second day, there are small improvements in Groups A, B and C but not in Group D. None of these group trends is statistically significant although the mean value in Group D is significantly higher than those in Group B (P<0.01) and C (P<0.02). There is no significant inter-group

349

350

BRITISH JOURNAL OF ANAESTHESIA

TABLE IX.

included to allow comparison with an earlier study (Spence and Smidi, 1971). Group E was added to determine die extent to which die findings in Groups B and C were specific to pentazocine. Patients who were given analgesics by regular injections or by infusion received considerably more drug than those in odier regimens. However, diere was only a marginal improvement in their pulmonary gas exchange compared to tiiose on more conventional medication, die results in die five groups having similar clinical significance. Prior to dus study, it would have been reasonable to suppose diat die use of larger amounts of analgesics would have modified die postoperative changes in pulmonary function. On die one hand, one might expect improvement. The larger amounts of analgesics used would be expected to produce more profound or more prolonged analgesia, and Spence and Smidi (1971) were able to equate die improved analgesia diey obtained

Details of male patients in Group E who received morphine 10 mg i.m. every 4 hours for 48 hours following vagotomy and drainage.

Number Mean 13 SEM TABLE X.

Age

(yr) 40.6 ±2.4

Height (cm) 172.0

Weight (kg) 66.0

±2.0

±2.7

Amount of

Amount of Tobacco consumption morphine given (cigarettes/ in 24 hours day) (mg) 55.5 14.7

morphine given

in 48 hours (mg) 100.9 ±6.1

±2.1

±2.5

Arterial gas tensions and lungvolumes of patients in Group E before

and after operation (±SEM). Preop, day

Pacoi (mm Hg) Paoi (mm Hg) (A-a)Po, (mm Hg) Change in (A-a)Po , (mmHg) FRC postop./FRC preop. (%) VC postop./VC preop. (%)

37.3 ±0.9 88.6 ±2.4 13.6

±2.3 —

— —

Postoperative days 1

DISCUSSION

5

±3.0

±4.0

±2.9

±3.0

±3.1

±4.5

±7.9 52.9 ±5.5

±2.9 99.5 ±7.2

±2.5 25.9 ±3.5 14.4

74.4 45.7

±4.4 Pentazocine was selected as die principal drug in this study because it is an example of a powerful analgesic (Keats and Telford, 1964) which is relatively free from abuse and exempt from die Dangerous Drugs Act. This latter advantage helped gready in securing die co-operation of our surgical and nursing colleagues. The morphine Group D was

2

39.2 ±1.7 72.3 ±3.0

39.9 ±1.2 72.5

26.9

12.3

85.5

36.4 ±1.0 89.1

14.0 1.5

77.2

±4.5

from continuous extradural nerve block widi improved postoperative lung function. We consider diat much of die effect of postoperative pain on lung function results from abdominal muscle spasm which compresses die lungs and reduces FRC (Spence and Alexander, 1972). The reduction of FRC has been shown to be related to die postoperative increase in alveolar/arterial oxygen tension difference (Alexan-

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the postoperative VC expressed as a percentage of the preoperative value. There is less reduction of VC on die second postoperative day in Group C than in Group B (P<0.03). Table IX shows details of 13 additional patients who received morphine 10 mg ijn. every 4 hours for 48 hours postoperatively. Their mean age, weight, height and cigarette consumption are similar to those of die patients in die principal study. The effect of operation on die arterial blood gases and lung volumes is shown in table X. The Pa, increased following operation and is significandy higher on die first 2 postoperative days dian preoperatively (P<0.03). Compared to Group D, die mean Paoa is higher and die mean (A-a)Po, diff. lower, on die preoperative day and diroughout die period of measurement (P<0.05). The rise in (A-a)Po, diff. after operation is smaller in diis group and is significandy different from die rise in Group D on the second day (P<0.02).

POSTOPERATIVE ANALGESIA AND LUNG FUNCTION

ACKNOWLEDGEMENTS

This work was supported by a grant from the Secretary of State for Scotland We are grateful to the Board of Management for Glasgow Western and Gartnavel Hospitals for help with the purchase of equipment. We wish to

thank our surgical and nursing colleagues for their cooperation, Miss Martha Woodburn for secretarial, and Mr Hugh Gorman for technical assistance. REFERENCES

Alexander, J. I., Spence, A. A., Parikh, R, K., and Stuart, B. (1973). The role of airway closure in postoperative hypoxaemia. Brit. J. Anaetih., 45, 34. Beecher, H. K. (1965). Quantification of the subjective pain experience. Proc Amer. psychopath. Ass., 53, 111. Egbert, L. D., and Bendixen, H. H. (1964). Effect of morphine on breathing pattern. J. Amer. med. Ass., 188, 485. Ellison, L. T., Duke, T. F., Strickland, G. W., and Ellison, R. G. (1966). Oxygen requirements in the early postoperative period (48 hours): ventilation and respiratory exchange. Ann. Surg., 163, 559. Goodman, L. S., and Gilman, A. (1965). The Pharmacological Basis of Therapeutics (3rd edn.) p. 247. New York: Macmillan. Herrald, F. J. C , and McMichael, J. (1939). Determination of lung volume: a simple constant volume modification of Christie's method. Proc roy. Soc. B., 126, 491. Keats, A. S., and Telford, J. (1964). Studies of analgesic drugs. VIII: A narcotic antagonist analgesic without psychotomimetic effects. J. Pharmacol, exp. Ther., 143, 157. Kelman, G. R., Nunn, J. F., Prys-Roberts, G, and Greenbaum, R, (1967). The influence of cardiac output on arterial oxygenation: a theoretical study. Brit. J. Anaesth., 39,450. Lasagna, L., and Beecher, H. K. (1954). The optimal dose of morphine. J. Amer. med. Ass., 156, 230. Lundin, G. (1953). Nitrogen elimination during oxygen breathing. Ada physiol. scand., suppL 111, 130. Muller, G. P., Overholt, R. H-, and Pendergrass, E. P. (1929). Postoperative pulmonary hypoventilation. Arch. Surg., 19, 1322. Severinghaus, J. W. (1966). Blood gas calculator. J. appl. Physiol, 21, 1108. Spence, A. A., and Alexander, J. I. (1972). Mechanisms of postoperative hypoxaemia. Proc roy. Soc. Med., 65, 12. Smith, G. (1971). Postoperative analgesia and lung function: a comparison of morphine with extradural block. Brit. J. Anaesth., 43. 144.

ANALGESIE POSTOPERATOIRE ET FONCTION PULMONAIRE: UNE COMPARAISON DE REGIMES ANALGESIQUES NARCOTIQUES SOMMATJtE

Quatre-vingt neuf homines, subissant une vagotomie elective avec drainage, ont txi distribute parmi deux (troupes de methode cfanalgesie narcotique postopeiaioire. L'analgeste etait administree, soit par voie tntramusculaire lorsque necessaire, soit regulierement par voie intramusculaire ou par infusion intraveineuse continue. En depit du fait qu ft y cut une difference considerable entre les quantites totales de medicament, adminlstrees suivant ces deux methodes, les differences de l'echange de gaz pulmonaire ou des volumes pulmonaires ne furent que marginales.

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der et al., 1973). On the basis of FRC measurements, none of the regimens was different from the rest in respect of muscle spasm. Others would attach more importance to the eradication of the sharp pain which inhibits coughing (Muller, Overholt and Pendergrass, 1929). Our impression was that this type of pain persisted in every patient. On die other hand, it could have been argued that lung function would deteriorate. Lasagna and Beecher (1954) have shown that high dose analgesic medication can produce an increased frequency of undesirable side-effects without any improvement in pain relief. Egbert and Bendixen (1964) warn of the dangers of drug-induced inhibition of coughing, central depression and ventilatory failure. Our observations indicate that the size and frequency of analgesic doses used in this study did not produce these effects. We have assumed that die measured changes in alveolar/arterial oxygen tension difference are exclusively a function of intrapulmonary shunt. A reduction in mixed venous oxygen content, resulting from either a fall in cardiac output or a rise in total oxygen consumption, would cause a deterioration in alveolar/arterial oxygen tension difference for any given amount of intrapulmonary shunt (Kelman et al., 1967). The routine ward measurements of pulse rate and arterial blood pressure did not suggest any cardiovascular disturbance in any group. However, we have insufficient data to comment further on this possibility. There are formidable difficulties in assessing pain relief (Beecher, 1965) and the large errors inherent in the available methods demanding large numbers of patients. This study is based on relatively small numbers and therefore no attempt has been made to report die analgesic effect of the different regimens. The practical importance of these findings must depend on whether subjective pain relief is improved by increased amounts of analgesics. For what it is worth, our clinical impression and that of our surgical and nursing colleagues, is that patients on the regular analgesic regimens were more comfortable while not presenting any problems of nursing management. Certainly, it would now seem appropriate to explore this possibility in a study of analgesimetry.

351

BRITISH JOURNAL OF ANAESTHESIA

352 POSTOPERATIVE ANALGESIE UND LUNGENFUNKTION: EIN VERLEICH VON VERFAHREN FOR NARKOTISCHE ANALGESIE

ANALGESIA POSTOPERATORIA Y FUNCION PULMONAR: COMPARACION DE DISTINTOS REGIMENES ANALGESICOS NARCOTICOS

ZUSAMMENFASSUNG

Se asign6 uno de dos metodos de anestesia narcotica postoperatoria a 89 hombres en los cuales se realizo una vagotomia electiva con drenaje. La analgesia tut administrada intramuscularmente, a petition de los pacientes, o de un modo regular por inyeccion intramuscular o por infusion endovenosa continua. Aunque hubo unas diferencias considerables en las cantidarirs totales del farmaco que fueron administradas por cada uno de estos dos metodos, solamente se produjeron diferencias marginales por lo que respecta a los volores de intercambio gaseoso pulmonar o en los volumenes pulmonares.

RESUMEN

89 Patienten, welche sich einer selectiven Vagotomie und DrSnage unterzogen, wurden nach einer von zwei Methoden der postoperariven narkotischen Analgesic eingeteilt. Entweder wurden die Analgetica intramuskular nach Aufforderung vcrabreicht oder die Zufuhr erfolgte regelmfifiig mittels intramuskulirer Injektion oder kontinuierlicher intravenoser Infusion. Obwohl sich ein erhebicher Unterschied der Gesamtmengen von Medikamenten, welche nach diesen beiden Methoden verabreicht wurden, ergab, stelhen sich doch nur geringgradige Unterschiede des pulmonalen Gasaustausches oder des Lungenvolumens heraus.

Throughout processing of these data the logic net continued to operate, suggesting strongly that a genuine point Sir,—We are grateful for the opportunity of replying to of inflection was being observed. Furthermore, this same the comments by Drs Prys-Roberts and Fo6x (Brit. J. conditional statement for gating of the LVEDP point Anaesth. (1973), 45, 121) on our recent papers (Bn'f. J. would not have been fulfilled if the recording system were excessively damped. For these reasons we do not accept Anaesth. (1971), 43, 25, and (1972) 44, 1006). correspondents' suggestion that these observations May we first reiterate that the chief purpose of our your artefacts. As regards an explanation for the finding, we experiments was to assess the haemodynamic effects of are nothing to add to our earlier suggestion (Bn'f. J. beta-blockade in an experimental preparation designed to have simulate as closely as possible conditions encountered Anaesth., 44, 1013). Drs Prys-Roberts and Foex would probably agree during clinical anaesthesia. The likely clinical indication for beta-blockade is, of course, adrenergic overactiviry, and that the experimental manoeuvres required to obtain venfor this reason we cannot accept the suggestion of your tricular function curves would be likely to complicate correspondents that our animalu were unsuitable as con- matters considerably, and that where, for example, introls on the grounds of sympathetic overactiyity: on the creased stroke work is associated with reduced filling contrary, the observations in this group of animals appear pressure, this may be accepted as qualitative evidence of increased performance: the plotting of full function curves to us highly relevant to the purpose of the study. however be an advantage in those instances where The fact that in Dr Prys-Roberts' patients (1969) receiv- might reductions both of stroke work and of filling ing beta-blockade for sympathetic overactivity, cardiac out- combined might conceal a decrease in performance in addiput and right atrial pressure returned to normal rather pressure than depressed levels would only suggest to us that myo- tion to reduced venous return. We appreciate the interest your correspondents have cardial depressant factors such as acidosis, hypoxia and expressed in our paper, and acknowledge the validity of hypercapnia were absent in these patients. of their comments. However, we wish to emphasize Your correspondents' findings in no way conflict with some again that our purpose was to draw attention to the likely our suggestion that beta-blockade should not be risked effects beta-blockade on cardiac performance under where there is hypercarbia, acidosis or oligaemia: our clinical of conditions: our contention is not that these agents reservations are based partly on the present studies and themselves myocardial depression, but that they are partly on the very profound effects of beta-blockade on capable of cause the normal adrenergic response to contractility which we have observed in dogs subjected to myocardial abolishing depressant agents. Thus we remain unable to experimental oligaemia. ourselves that beta-blockade is a safe procedure We are in broad agreement with Drs Prys-Roberts and satisfy sympathetic overactivity exists and hypercapnia or FoSx in respect of some of their comments on the where acidosis have not been excluded as causes for this. measurement of dP/dt max and its possibly limited value While your correspondents may feel that the case as an index of cardiac performance where heart rate and filling pressure are subject to variation: the dependence of against beta-blockade remains unproven, we would suggest dP/dt TTIHT on heart rate is of course widely recognized, that the clinical case for the use of beta-blockade is by no although your correspondents* figure demonstrating a means proven, although this latter argument falls a little 16-17% increase in dP/dt in response to a 44% heart outside the scope of the present correspondence. May we rate increase is perhaps something less than the "strong" in conclusion draw your attention, sir, to another legal dependence they imply. However, we believe that our principle—doubtless common to Rnglish and Scots law— initial values of LVEDP in the dogs receiving practolol are "caveat emptor". entirely valid: throughout processing the crude pressure A. J. STRONG I. T. DAVTB traces were regularly inspected with the oscilloscope time D. B. SCOTT M. F. MACNICOL base set for fast sweep. Although a completely flat endEdinburgh diastolic plateau was difficult to establish, and might not REFERENCE invariably be expected at high heart rate, the conditional statements in the computer logic specifying the end- Prys-Roberts, C, Corbett, J. L., Kerr, J. H., Crampton diastolic point included the requirement that the second Smith, A., and Spalding, J. M. K. (1969). Treatment of derivative of pressure should exceed 300 mm Hg sec- 1 . sympathetic overactivity in tetanus. Lancet, 1, 542. BETA-BLOCKADE AND LEFT VENTRICULAR PERFORMANCE UNDER HALOTHANE ANAESTHESIA

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CORRESPONDENCE