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DURATION OF FAST BEFORE ELECTIVE SURGERY
Br. J. Anaesth. (1985), 57, 1038-1046
CORRESPONDENCE
LABORATORY DIAGNOSIS OF MALIGNANT HYPERPYREXIA SUSCEPTIBILITY (MHS)
criteria. The laboratory test limits were purposely set to restrict the diagnosis of MHS and M H N to those patients whose laboratory results would be universally acceptable; both of these diagnoses are of great clinical importance and potential danger. An extended MHE group provided a degree of security for the patients because it was agreed that most of these patients would be reported as MH susceptible in the clinical context. MHN 183
MHE 91
EUROPEAN MH
MHS 75
1
2 3 4 " >4 Caffeine (nrmol litre"1) FIG. I. Diagnostic grouping of 349 patients according to original criteria.
MHN 202
GROUP
(Correspondence to F. R. Ellis, Secretary to the European Group, Dept. of Anaesthesia, St. James's University Hospital, Leeds LS9 7TF.) REFERENCES Ellis, F. R. (1984). European malignant hyperpyrexia group. BT. J. Anaesth., 56, 1183. European MH Group (1984). A protocol for the investigation of malignant hyperpyrexia (MH) susceptibility. Br. J. Anaesth., 56, 1267.
DURATION OF FAST BEFORE ELECTIVE SURGERY
1
2
3
4
>4
Caffeine (mnxil fare"1) FIG. 2. Re-grouping of the 349 patients according to new diagnostic limits.
Sir,—Miller, Wishart and Nimmo (1983) reported that consumption of a light breakfast was not contraindicated before surgery and general anaesthesia in light of their findings of no difference between the volume or pH of gastric contents in a fed population compared with a fasted population. In their conclusion they imply that a pH of 3.0 is safe when discussing aspiration of gastric contents.
Downloaded from http://bja.oxfordjournals.org/ at Harvard University on July 27, 2015
Sir,—Confirmation of clinical diagnosis of malignant hyperpyrexia (MH) and the subsequent family investigation of relatives of MH patients depends at present on a laboratory study of living muscle tissue. Until recently, each laboratory has determined its own limits of normality from control data which are difficult to obtain. The European MH Group encouraged all member departments to adopt the same experiment procedure, enabling a more rapid collection of comparable data than any individual department could have achieved in the same time. The paper reporting the new diagnostic criteria (European MH Group, 1984) described three categories of patient, namely MHS (patients undoubtedly susceptible to MH), MHN (patients undoubtedly not susceptible to MH) and MHE, whose laboratory results were equivocal according to the new
Whilst the fundamental importance of the MHE category was recognized when the protocol was published (Ellis, 1984), it was stated than that this category would be subject to "permanent review", and would be reduced in proportion in the light of experience. If the inheritance of MH is accepted as a dominant characteristic, there should be no equivocal MHE category, as heterozygotes would be identified as MHS and hornozygote normals as MHN. The MHE result must represent a "grey area" of diagnosis which has no genetic relevance. Combining results obtained by member units of the European MH Group since the acceptance of the protocol, 349 patients were diagnostically grouped as follows: 75 (22%) as MHS; 183 (52%) as MHN; 91 (26%) at MHE (fig. 1). Following a review of all 91 MHE patients, and comparing the laboratory result with the case material and the family relationships, it was agreed to adjust the diagnostic limits to those shown in figure 2, namely: MHS: a halothane contracture at 2 % v/v or less AND a caffeine contracture at 2 mmol litre"1 or less; MHN: no halothane contracture at 2% v/v or less AND no caffeine contracture at 2 mmol litre"1 or less; MHE: all other results. This revision can be seen, first, to have rationalized the diagnostic limits between the three categories and, second, to have almost halved the MHE group from 91 to 51 patients (15%). Of the 40 patients removed from the MHE group, 21 have been incorporated into the MHS group, and 19 into the MHN group. It is still envisaged that many of the MHE patients should be accepted as clinically susceptible to MH, pending further elucidation.
CORRESPONDENCE
1039
M. Sosis M. GOLDBERG
Philadelphia REFERENCES Mendelson, C. L. (1946). The aspiration of stomach contents into the lungs during obstetric anesthesia. Am. J. Obstet. Gynecol., 52, 191. Miller, M., Wishart, H. Y., and Nimmo, W. S. (1983). Gastric contents at induction of anaesthesia. Br. J. Anaetth., 55, 1185. Moran, T. J. (1951). Experimental food aspiration pneumonia. Arch. Pathol., 52, 350. Schwartz, D. J., Wynne, J. W., Gibbs, C. P., Hood, I. C , Kuck, E. J. (1980). The pulmonary consequences of aspiration of gastric contents at pH values greater than 2.5. Am. Rev. Resp. Dis., 121, 119. Wynne, J. W., Reynolds, J. C , Hood, C. I., Averbach, D., and Ondrasick, J. (1979). Steroid therapy for pneumonitis induced in rabbits by aspiration of foodstuff. Anesthesiology, 51, 11. Sir,—Thank you for allowing me to comment on the letter from Drs Goldberg and Sosis. Although I do not wish to reply specifically to the points raised in their letter, I would take issue with the last sentence of their first paragraph. I would point out to your readers that we did not imply that a pH of 3.0 is safe when one is discussing aspiration of gastric contents. W. S. NIMMO
Sheffield
PARACETAMOL KINETICS AND GASTRIC EMPTYING Sir,—We are investigating immediate post-partum gastric function and the influence of metoclopramide on it, using paracetamol absorption kinetics as a measure of gastric emptying (Heading eta]., 1973, Clements etal., 1978;Nimmo, 1978). Murphy and colleagues (1984) describe the effects of metoclopramide on gastric emptying in pregnant patients also
using paracetamol absorption as a marker. Their application of this useful method is, however, suspect. Nimmo and colleagues (1975) demonstrated a correlation coefficient of 0.94 between the amount of paracetamol absorbed over 1 h (i.e. area under the plasma concentration curve after 1 h) and gastric emptying. A single sample at a fixed time, as used by Murphy and colleagues (1984) cannot be an accurate reflection of the amount absorbed, as one has no knowledge of curve profiles. Rapid absorption (or emptying) could result in a sampling during the downstroke of the curve and slow absorption (or emptying) during the upstroke. Comparisons of results obtained by single "spot" sampling are therefore invalid. The influence of metoclopramide on gastric emptying in the presence of opioids remains unclear and deserves further study. B. A. FINNEGAN C. A. JYN
Saskatoon
REFERENCES Clements, J. A., Heading, R. C , Nimmo, W. S., and Prescott, L. F. (1978). Kinetics of acetaminophen absorption and gastric emptying in man. Clin. Pharmacol. Ther., 24, 420. Heading, R. C , Nimmo, J., Prescott, L. F., and Tothill, P. (1973). The dependence of paracetamol absorption on the rate of gastric emptying. Br. J. Pharmacol., 47, 415. Murphy, D. F., Nally, B., Gardiner, J., and Unwin, A. (1984). Effect of metoclopramide on gastric emptying before elective and emergency Caesarean section. Br.J.Anaesth., 56,1113. Nimmo, W. S. (1978). The measurement of gastric emptying during labour. J. Int. Med. Res., 6, (Suppl. 1), 52. Heading, R. C , Wilson, J., Tothill, P., and Prescott, L. F. (1975). Inhibition of gastric emptying and drug absorption by narcotic analgesics. Br. J. Clin. Pharmacol., 2, 509.
Sir,—Thank you for allowing us the opportunity to reply to Drs Finnegan and Jyn who take issue with the methodolology used in our study of gastric emptying in pregnant patients. In the original work, Heading and colleagues (1973) related the rate of gastric emptying, as measured by a sequential scintiscanning technique, to paracetomol absorption. In all cases, peak plasma paracetamol concentrations are quoted and not "area under curve" ( A U Q estimations. These results showed that "there were (also) statistically significant correlations between the half-time of gastric emptying and the plasma concentration at 30 min and at 60 min." All subsequent studies by these authors (Nimmo et al., 1973; Nimmo, Wilson and Prescott, 1975;Nimmoetal., 1975;Nimmo, 1978; Wilson, 1978) quote mean peak plasma concentrations in their results. There is one reference to plasma concentration-time, area under curve estimation (figure 4, Nimmo et al., 1975) and it is assumed that it is in reference to this that Drs Finnegan and Jyn believe AUC estimations should be used. For our study, we accepted the validity of the "paracetamol absorption " technique and used mean peak plasma paracetamol concentrations as an indirect index of the rate of gastric emptying. We do not, therefore, accept that the methodology used is invalid. It is possible that AUC estimations might be a better method of analysis, but would certainly be more difficult to undertake and control in labouring patients. In any event, it is our opinion that the plasma paracetamol
Downloaded from http://bja.oxfordjournals.org/ at Harvard University on July 27, 2015
We believe that aspiration of food particles is hazardous even when the pH is >2.5. Wynne and associates (1979) demonstrated that the aspiration of paniculate gastric contents at a pH of 4.3 was associated with severe lung injury. Moran (1951) found the pathological changes caused by non-acidic ground food aspiration in the guineapig to be identical to food aspiration pneumonia in man. Schwartz and co-workers (1980) add further support to this contention by demonstrating that aspiration of gastric contents with a pH of 5.9 was associated with changes consistent with pneumonitis. These findings on paniculate matter may contradict the classic findings on Mendclson's syndrome (Mendelson, 1946). Miller's study does not examine the effect of a light breakfast on the amount of paniculate matter in the stomach. The discomfort involved in fasting seems insignificant compared with the risks incurred by aspiration of foods. Aspiration of paniculate matter clearly can be associated with severe morbidity and should be avoided. We therefore encourage the continued practice of fasting patients for at least 4 h before elective surgery.
CORRESPONDENCE
LABORATORY DIAGNOSIS OF MALIGNANT HYPERPYREXIA SUSCEPTIBILITY (MHS)
criteria. The laboratory test limits were purposely set to restrict the diagnosis of MHS and M H N to those patients whose laboratory results would be universally acceptable; both of these diagnoses are of great clinical importance and potential danger. An extended MHE group provided a degree of security for the patients because it was agreed that most of these patients would be reported as MH susceptible in the clinical context. MHN 183
MHE 91
EUROPEAN MH
MHS 75
1
2 3 4 " >4 Caffeine (nrmol litre"1) FIG. I. Diagnostic grouping of 349 patients according to original criteria.
MHN 202
GROUP
(Correspondence to F. R. Ellis, Secretary to the European Group, Dept. of Anaesthesia, St. James's University Hospital, Leeds LS9 7TF.) REFERENCES Ellis, F. R. (1984). European malignant hyperpyrexia group. BT. J. Anaesth., 56, 1183. European MH Group (1984). A protocol for the investigation of malignant hyperpyrexia (MH) susceptibility. Br. J. Anaesth., 56, 1267.
DURATION OF FAST BEFORE ELECTIVE SURGERY
1
2
3
4
>4
Caffeine (mnxil fare"1) FIG. 2. Re-grouping of the 349 patients according to new diagnostic limits.
Sir,—Miller, Wishart and Nimmo (1983) reported that consumption of a light breakfast was not contraindicated before surgery and general anaesthesia in light of their findings of no difference between the volume or pH of gastric contents in a fed population compared with a fasted population. In their conclusion they imply that a pH of 3.0 is safe when discussing aspiration of gastric contents.
Downloaded from http://bja.oxfordjournals.org/ at Harvard University on July 27, 2015
Sir,—Confirmation of clinical diagnosis of malignant hyperpyrexia (MH) and the subsequent family investigation of relatives of MH patients depends at present on a laboratory study of living muscle tissue. Until recently, each laboratory has determined its own limits of normality from control data which are difficult to obtain. The European MH Group encouraged all member departments to adopt the same experiment procedure, enabling a more rapid collection of comparable data than any individual department could have achieved in the same time. The paper reporting the new diagnostic criteria (European MH Group, 1984) described three categories of patient, namely MHS (patients undoubtedly susceptible to MH), MHN (patients undoubtedly not susceptible to MH) and MHE, whose laboratory results were equivocal according to the new
Whilst the fundamental importance of the MHE category was recognized when the protocol was published (Ellis, 1984), it was stated than that this category would be subject to "permanent review", and would be reduced in proportion in the light of experience. If the inheritance of MH is accepted as a dominant characteristic, there should be no equivocal MHE category, as heterozygotes would be identified as MHS and hornozygote normals as MHN. The MHE result must represent a "grey area" of diagnosis which has no genetic relevance. Combining results obtained by member units of the European MH Group since the acceptance of the protocol, 349 patients were diagnostically grouped as follows: 75 (22%) as MHS; 183 (52%) as MHN; 91 (26%) at MHE (fig. 1). Following a review of all 91 MHE patients, and comparing the laboratory result with the case material and the family relationships, it was agreed to adjust the diagnostic limits to those shown in figure 2, namely: MHS: a halothane contracture at 2 % v/v or less AND a caffeine contracture at 2 mmol litre"1 or less; MHN: no halothane contracture at 2% v/v or less AND no caffeine contracture at 2 mmol litre"1 or less; MHE: all other results. This revision can be seen, first, to have rationalized the diagnostic limits between the three categories and, second, to have almost halved the MHE group from 91 to 51 patients (15%). Of the 40 patients removed from the MHE group, 21 have been incorporated into the MHS group, and 19 into the MHN group. It is still envisaged that many of the MHE patients should be accepted as clinically susceptible to MH, pending further elucidation.
CORRESPONDENCE
1039
M. Sosis M. GOLDBERG
Philadelphia REFERENCES Mendelson, C. L. (1946). The aspiration of stomach contents into the lungs during obstetric anesthesia. Am. J. Obstet. Gynecol., 52, 191. Miller, M., Wishart, H. Y., and Nimmo, W. S. (1983). Gastric contents at induction of anaesthesia. Br. J. Anaetth., 55, 1185. Moran, T. J. (1951). Experimental food aspiration pneumonia. Arch. Pathol., 52, 350. Schwartz, D. J., Wynne, J. W., Gibbs, C. P., Hood, I. C , Kuck, E. J. (1980). The pulmonary consequences of aspiration of gastric contents at pH values greater than 2.5. Am. Rev. Resp. Dis., 121, 119. Wynne, J. W., Reynolds, J. C , Hood, C. I., Averbach, D., and Ondrasick, J. (1979). Steroid therapy for pneumonitis induced in rabbits by aspiration of foodstuff. Anesthesiology, 51, 11. Sir,—Thank you for allowing me to comment on the letter from Drs Goldberg and Sosis. Although I do not wish to reply specifically to the points raised in their letter, I would take issue with the last sentence of their first paragraph. I would point out to your readers that we did not imply that a pH of 3.0 is safe when one is discussing aspiration of gastric contents. W. S. NIMMO
Sheffield
PARACETAMOL KINETICS AND GASTRIC EMPTYING Sir,—We are investigating immediate post-partum gastric function and the influence of metoclopramide on it, using paracetamol absorption kinetics as a measure of gastric emptying (Heading eta]., 1973, Clements etal., 1978;Nimmo, 1978). Murphy and colleagues (1984) describe the effects of metoclopramide on gastric emptying in pregnant patients also
using paracetamol absorption as a marker. Their application of this useful method is, however, suspect. Nimmo and colleagues (1975) demonstrated a correlation coefficient of 0.94 between the amount of paracetamol absorbed over 1 h (i.e. area under the plasma concentration curve after 1 h) and gastric emptying. A single sample at a fixed time, as used by Murphy and colleagues (1984) cannot be an accurate reflection of the amount absorbed, as one has no knowledge of curve profiles. Rapid absorption (or emptying) could result in a sampling during the downstroke of the curve and slow absorption (or emptying) during the upstroke. Comparisons of results obtained by single "spot" sampling are therefore invalid. The influence of metoclopramide on gastric emptying in the presence of opioids remains unclear and deserves further study. B. A. FINNEGAN C. A. JYN
Saskatoon
REFERENCES Clements, J. A., Heading, R. C , Nimmo, W. S., and Prescott, L. F. (1978). Kinetics of acetaminophen absorption and gastric emptying in man. Clin. Pharmacol. Ther., 24, 420. Heading, R. C , Nimmo, J., Prescott, L. F., and Tothill, P. (1973). The dependence of paracetamol absorption on the rate of gastric emptying. Br. J. Pharmacol., 47, 415. Murphy, D. F., Nally, B., Gardiner, J., and Unwin, A. (1984). Effect of metoclopramide on gastric emptying before elective and emergency Caesarean section. Br.J.Anaesth., 56,1113. Nimmo, W. S. (1978). The measurement of gastric emptying during labour. J. Int. Med. Res., 6, (Suppl. 1), 52. Heading, R. C , Wilson, J., Tothill, P., and Prescott, L. F. (1975). Inhibition of gastric emptying and drug absorption by narcotic analgesics. Br. J. Clin. Pharmacol., 2, 509.
Sir,—Thank you for allowing us the opportunity to reply to Drs Finnegan and Jyn who take issue with the methodolology used in our study of gastric emptying in pregnant patients. In the original work, Heading and colleagues (1973) related the rate of gastric emptying, as measured by a sequential scintiscanning technique, to paracetomol absorption. In all cases, peak plasma paracetamol concentrations are quoted and not "area under curve" ( A U Q estimations. These results showed that "there were (also) statistically significant correlations between the half-time of gastric emptying and the plasma concentration at 30 min and at 60 min." All subsequent studies by these authors (Nimmo et al., 1973; Nimmo, Wilson and Prescott, 1975;Nimmoetal., 1975;Nimmo, 1978; Wilson, 1978) quote mean peak plasma concentrations in their results. There is one reference to plasma concentration-time, area under curve estimation (figure 4, Nimmo et al., 1975) and it is assumed that it is in reference to this that Drs Finnegan and Jyn believe AUC estimations should be used. For our study, we accepted the validity of the "paracetamol absorption " technique and used mean peak plasma paracetamol concentrations as an indirect index of the rate of gastric emptying. We do not, therefore, accept that the methodology used is invalid. It is possible that AUC estimations might be a better method of analysis, but would certainly be more difficult to undertake and control in labouring patients. In any event, it is our opinion that the plasma paracetamol
Downloaded from http://bja.oxfordjournals.org/ at Harvard University on July 27, 2015
We believe that aspiration of food particles is hazardous even when the pH is >2.5. Wynne and associates (1979) demonstrated that the aspiration of paniculate gastric contents at a pH of 4.3 was associated with severe lung injury. Moran (1951) found the pathological changes caused by non-acidic ground food aspiration in the guineapig to be identical to food aspiration pneumonia in man. Schwartz and co-workers (1980) add further support to this contention by demonstrating that aspiration of gastric contents with a pH of 5.9 was associated with changes consistent with pneumonitis. These findings on paniculate matter may contradict the classic findings on Mendclson's syndrome (Mendelson, 1946). Miller's study does not examine the effect of a light breakfast on the amount of paniculate matter in the stomach. The discomfort involved in fasting seems insignificant compared with the risks incurred by aspiration of foods. Aspiration of paniculate matter clearly can be associated with severe morbidity and should be avoided. We therefore encourage the continued practice of fasting patients for at least 4 h before elective surgery.