936
21. Otani
H, Engelman RM, Rousou JA, Breyer RH, Das DK. Enhanced susceptibility of immature hearts to free radical mediated reperfusion injury. In: Hayaishi O, Niki E, Kondo M, Yoshikawa T, eds. Medical, Biochemical and Chemical Aspects of Free Radicals. Amsterdam: Elsevier Science Publishers, 1989: 1181-84. 22. Thurnham DI, Koottathep S, Adelekan DA. Chain-breaking antioxidants in the blood of malaria infected children. In: Rice Evans C, Dormandy T, eds. Free radicals: chemistry, pathology and medicine. London: Richelieu Press, 1988: 161-85. 23.
Samokyszyn VM, Miller DM, Reif DW,
Aust SD. Inhibition of
24.
supcroxide and ferritin dependent lipid peroxidation by ceruloplasmin. J Biol Chem 1989; 264: 21-26. Lundh B, Oski FA, Gardner FH. Plasma hemopexin and haptoglobin in hemolytic diseases of the newborn. Acta Paediatr Scand 1970; 59:
121-26. 25. Chiu D, Kuypers F, Lubin B. Lipid peroxidation in human red cells. Semin Haematol 1989; 26: 257-76. 26. Hershko C. Mechanism of iron toxicity and its possible role in red cell membrane damage. Semin Haematol 1989; 26: 277-85. 27. Editorial. Oral iron chelators. Lancet 1989; ii: 1016-17.
Effect of
doxapram on postoperative pulmonary complications after upper abdominal surgery in high-risk patients
In
a
double-blind randomised trial
an
infusion of
doxapram, 2 mg per min for 6 h immediately after surgery and repeated on the first postoperative day, or the same volume of saline, was given to 39 patients who underwent upper abdominal surgery and who were at high risk of postoperative pulmonary complications. The patients were assessed pre-operatively and during the first 5 postoperative days by physical examination, spirometry, blood-gas analysis, and chest radiography. Postoperative pulmonary complications for 2
were
defined
as
temperature
over
38°C
days, abnormal auscultation, pathological radiograph, and/or productive cough. Data from 16 patients per group were analysed. Significantly more patients in the placebo group had three criteria of postoperative pulmonary complication compared with the doxapram group (63% vs 19%). The doxapram group also had higher PaO2 postoperatively. Lancet 1990; 335: 936-38.
Introduction
Pulmonary complications are the most common cause of morbidity and mortality after surgical operations. The frequency after laparotomy varies from 5% to 80%, depending on the type of operation and the definitions used for pulmonary complications; most workers agree on a frequency around 20% for healthy individuals. Despite many advances in anaesthesia, the frequency has not changed much over the past 40 years.Z Controversy exists as to whether the respiratory stimulant doxapram can reduce pulmonary complications after surgery.3-S However, no reported study looked at high-risk patients. We have examined the effect of doxapram on postoperative pulmonary complications in such patients after upper abdominal surgery.
Patients and methods Patients 39 patients who were admitted for elective surgery involving the stomach, biliary tract, pancreas, colon, or kidney with incisions above the umbilicus and who fulfilled at least one of the following risk factors (lung disease with "functional dyspnoea" within the past 12 months, lung disease with cough and expectoration within the past 12 months, smoker of more than 15 cigarettes per day, occupational exposure to dust, or body weight exceeding 20% of median weight for height6) entered the trial. Patients with thyrotoxicosis, epilepsy, pregnancy, or dementia were excluded. Patients gave informed consent and the protocol was approved by the local ethical committee as being in accordance with the declaration of Helsinki II. Premedication consisted of hyoscine and morphine. Anaesthesia was standardised and balanced (thiopentone/pancuronium/fentanyl/droperidol or midazolam/nitrous oxide). General anaesthesia was combined with epidural analgesia with 0-5% bupivacaine in 16 patients via an epidural catheter, which was used when required for administration of morphine for postoperative analgesia. On arrival in the recovery room, the patients received either an infusion of doxapram, 2 mg per min in 500 ml isotonic saline for 6 h, or the same volume of saline over 6 h. The infusion was repeated during the afternoon of the first postoperative day. Allocation to the two groups was randomised and the two solutions were given double-blind. In the recovery room all patients received oxygen by nasal tube (2-4 ml per min). Chest physiotherapy was given twice daily from the first
postoperative day. Assessments
Physical examination, measurement of temperature and respiration frequency, and arterial blood-gas analysis were done
ADDRESSES: Department of General Surgery K, (J E. Jansen, MD, A I Sorensen, MD, A Pedersen, MD) and Department of Anaesthesiology (O Naesh, MD, C. J. Erichsen, MD), Frederiksberg
Hospital, University of Copenhagen, Denmark. Correspondence to
Dr J E Jansen,
Fuglsangpark 65, DK-3520 Farum, Denmark
937
TABLE I-PATIENTS’ CHARACTERISTICS TRIAL
No of patients
or
median
TABLE II-POSTOPERATIVE PULMONARY COMPLICATIONS
(range)
before the
operation and on each of the first 5 days after the operation. With the patient sitting forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1)’ and peak flow were measured on the day before the operation and on the first and third postoperative days with a dry spirometer (’Spirotron’, Drager). All measurements were made with the patients breathing room air. The first set of measurements was made 24 h after the operation before administration of doxapram or placebo. Chest radiographs in two planes were taken preoperatively and on the third postoperative day. The radiographs were analysed by a radiologist who was unaware of the treatment group. At the end of the study the presence of expectoration and the number of days in bed were recorded.
Postoperative pulmonary complications
were
defined
as
the
presence of one or more of the following criteria: (1) morning body temperature above 38.0°C for at least 2 days, with no suspicion of focus outside the lungs; (2) abnormal auscultation not heard
preoperatively; (3) productive cough atelectasis
or
or
infiltration. On clinical
purulent sputum; or (4) suspicion of pulmonary
embolism, lung-perfusion scintigraphy was done. Statistics
NS = not
significant
shown in table n: doxapram administration resulted in a significant reduction in many of the criteria. Similarly, when the combination of criteria was analysed, there was a significant reduction in those patients with up to three combinations. Postoperatively respiratory frequency was higher in the controls compared with the doxapram group, but this difference was significant on day 2 only. The results of arterial oxygen analysis are summarised in the figure. The mean Pa02 postoperatively was 9-4 kPa (SD 1-45) in the doxapram group compared with 8-5 kPa (1-45) in the In addition Pa02 at day 5 in those controls (p < 0°0001). patients receiving doxapram was not significantly different from the preoperative value whereas Pa02 on this day in control patients was significantly lower than the preoperative value (p 0-02). The mean arterial PaC02 values are shown in table ill. There were no differences in mean PaC02 or pH between the two groups. The respiratory function tests did not show significant differences between the two groups (table IV). The median duration of postoperative hospital stay was 9 days (range 5-22) in the doxapram group and 10 days (3-22) in the controls. 7 controls stayed for more than 10 days in the ward compared with 2 from the doxapram group (not =
Differences between the doxapram group and the control group were tested with Fisher’s exact test. Blood-gas analysis and spirometry were compared with unpaired t tests.
Results 16 patients who received doxapram and 16 who received placebo were analysed (table I). All findings related to the diagnosis of postoperative pulmonary complication are
significant). TABLE III-MEAN
(SE) ARTERIAL PaC02 (kPa) BEFORE AND AFTER OPERATION
*Slgnlflcant difference from TABLE IV-MEAN
Mean (SE) Pa02 preoperatively (P) and
days.
on
first 5
postoperative
mean
value before operation
(SE) FEV,
in same
group
(p < 0 05)
BEFORE AND AFTER OPERATION
938
3 patients additionally had pulmonary embolism, 1 in the doxapram group and 2 in the control group. 1 control patient died on day Iof massive pulmonary embolism. 7 patients were excluded from analysis. Doxapram infusions were discontinued in 3 patients; in 1 because of tachycardia and in 2 because of transient hypertension. "Control" infusions were stopped in 2 patients because of tachycardia and cardiac arrhythmias. 2 more patients were excluded: 1 in the doxapram group because of ventilator treatment before he had received any doxapram, and 1 control withdrew after the infusions were completed (excluded because of lack of data). The 3 patients from the doxapram group who were excluded received 800, 640, and 200 mg of doxapram, respectively. None showed any sign of postoperative pulmonary complications, while 2 of the 3 excluded control patients had fever, productive cough, and abnormal auscultation postoperatively. There is no available information about such complications in the third patient.
Discussion
Postoperative pulmonary complications are thought to be a consequence of hypoventilation leading to microatelectasis, veno-arterial shunting, and stasis of secretion, which predisopose to pulmonary infection and collapse of the lung. It has been suggested that doxapram, by acting as a "pharmacologic sigh" and inducing transient hyperventilation, can reduce this vicious circle.7 Doxapram increases both the tidal volume and the arterial oxygen tension in fit patients after abdominal surgery.4,5,8,9 Doxapram may also significantly reduce the frequency of cough and purulent sputum.5,8 However, several investigators have failed to demonstrate reduction in postoperative pulmonary complications when clinical and radiological examinations were taken into account. 10,12,13 The most important "high-risk" factors for postoperative pulmonary complications are chronic lung disease with dyspnoea and expectoration, smoking, obesity, immobility, age, duration of anaesthesia, and upper abdominal surgery or thoracic surgery.2,14 We studied high-risk patients: all underwent upper abdominal surgery, 47 % had chronic lung disease, 50% smoked more than 15 cigarettes daily, 53% were more than 20% overweight, and over half of the patients had more than one risk factor. The reduction in postoperative morbidity by doxapram was between 30 and 50% depending on which of the four criteria was used. Abnormal auscultation was the most sensitive tool in the diagnosis of postoperative pulmonary complications, as has been found before. 15 Taking temperature more than 38.0°C for 2 days, abnormal auscultation, and lung infiltration as criteria of postoperative pneumonia, 7 control patients had pneumonia compared with none in the doxapram group (p < 0.01). Despite the differences in postoperative pulmonary complications we found no significant difference in postoperative hospital stay (2 controls asked to be discharged at day 4 and 5, respectively, despite treatment for pneumonia, and 1 control died of pulmonary embolism on day 11). Our results are in broad agreement with an early study from Brazil in which doxapram significantly reduced postoperative atelectasis.11 Steele et al16 have shown that doxapram reduced postoperative pulmonary complications by 27% in patients who had normal respiratory indices and who underwent extensive abdominal operations. In both these studies, in contrast to others, doxapram was administered beyond the first 6 h postoperatively because
postoperative hypoxaemia can be protracted. In our study doxapram was administered by infusion immediately after surgery and on the first postoperative day. Taking postoperative pneumonia or combinations of up to three of our criteria of postoperative pulmonary complications into consideration, we found that the overall reduction in postoperative pulmonary morbidity produced by doxapram was 44% (20-70%). REFERENCES 1. Barlett RH. Pulmonary pathophysiology in surgical patients. Surg Clin North Am 1980; 60: 1323. 2. Garibaldi RA, Britt MR, Coleman ML, Reading JC, Pace NL. Risk factors for postoperative pneumonia. Am J Med 1981; 70: 677-80. 3. Anderson R, Krogh K. Post-operative analgesia combined with doxapram. Anaesthesia 1976; 31: 114. 4. Downing JW, Jeal DE, Allen PJ, Buley R. IV Doxapram hydrochloride and pulmonary complications after lower abdominal surgery. Br J Anaesth 1977; 49: 473-77. 5. Gawley TH, Dundee JW, Gupta PK, Jones CJ. Role of doxapram in reducing pulmonary complications after major surgery. Br Med J 1976; i: 122-24. 6. Natvig H. Nye Høyde-vekt-tabeller for norske kvinner og menn. Oslo: Landsforeningen for kosthold og helse, 1956. 7. Winnie AP, Gladisch JT, Angel JJ, Ramamurthy S, Collins VJ. Chemical respirogenesis II: reversal of postoperative hypoxemia with the "Pharmacologic Sigh". Anesth Analg 1971; 50: 1043-55. 8. Gupta PK, Dundee JW. The effect of an infusion of doxapram on morphine analgesia. Anaesthesia 1974; 29: 40-43. 9. Less NW, Howie HB, Mellon A, McKee AH, McDiarmid IA. The influence of doxapram on postoperative pulmonary function in patients undergoing upper abdominal surgery. Br J Anaesth 1976; 48: 1197-200. 10. Drummond GB, Park GR. Doxapram and postoperative chest complications. Anæsthesia 1983; 38: 3-6. 11. Plemont CB, Bibas RA, Campos RL, Guedes AHL. Prophylaxis of postoperative pulmonary atelectasis with Doxapram. Rev Brasil Anest 1970; 20: 1-14. 12. Hollway TE, Standford BJ. Effect of doxapram on postoperative oxygenation in obese patients. Anaesthesia 1982; 37: 718-21. 13. Sebel PS, Kershaw EJ, Rao WS. Effects of doxapram on postoperative pulmonary complications following thoracotomy. Br J Anæsth 1980; 52: 81-84. 14. Hechtman HB, Krausz MM, Utsonomiya T, Valeri CR. Preoperative assessment of high risk surgical patient. Surg Clin North Am 1980; 60: 1349-58. 15. Hansen G, Drabløs PA, Steinert R. Pulmonary complications, ventilation and blood gases after upper abdominal surgery. Acta Anæsth Scand 1977; 21: 211-15. 16. Steele RC, Walker WS, Irvine MKA. The use of doxapram in the prevention of postoperative pulmonary complications. Surg Gynecol Obstet 1982; 154: 510-12.
From The Lancet The case of Joseph Merrick at the London Hospital
Joseph Merrick, the so-called "Elephant man," died on Friday, the 11 th inst. He had been exhibited about the country for some time till the case attracted the attention of the authorities of the London Hospital, who offered him a shelter within their walls. It seems that on Thursday last the man was out in the garden apparently quite well. On Friday, at 1.30 pm, he was seen for the last time in his room alive, and at 3 pm he was discovered dead. Death was probably due to the falling back of the head, which was of enormous weight. Merrick has been the subject of many accounts, especially in American papers, and has been visited by half the celebrities in London. In 1886, as he was being exhibited in the East-end of London, he was seen by Mr Treves, who henceforward kept him under observation, and who has done much to contribute to the comfort of the unfortunate man. One of the greatest undertakings connected with the "Elephant man" was getting him into a theatre without his being discovered.
(19 April 1890)
21. Otani
H, Engelman RM, Rousou JA, Breyer RH, Das DK. Enhanced susceptibility of immature hearts to free radical mediated reperfusion injury. In: Hayaishi O, Niki E, Kondo M, Yoshikawa T, eds. Medical, Biochemical and Chemical Aspects of Free Radicals. Amsterdam: Elsevier Science Publishers, 1989: 1181-84. 22. Thurnham DI, Koottathep S, Adelekan DA. Chain-breaking antioxidants in the blood of malaria infected children. In: Rice Evans C, Dormandy T, eds. Free radicals: chemistry, pathology and medicine. London: Richelieu Press, 1988: 161-85. 23.
Samokyszyn VM, Miller DM, Reif DW,
Aust SD. Inhibition of
24.
supcroxide and ferritin dependent lipid peroxidation by ceruloplasmin. J Biol Chem 1989; 264: 21-26. Lundh B, Oski FA, Gardner FH. Plasma hemopexin and haptoglobin in hemolytic diseases of the newborn. Acta Paediatr Scand 1970; 59:
121-26. 25. Chiu D, Kuypers F, Lubin B. Lipid peroxidation in human red cells. Semin Haematol 1989; 26: 257-76. 26. Hershko C. Mechanism of iron toxicity and its possible role in red cell membrane damage. Semin Haematol 1989; 26: 277-85. 27. Editorial. Oral iron chelators. Lancet 1989; ii: 1016-17.
Effect of
doxapram on postoperative pulmonary complications after upper abdominal surgery in high-risk patients
In
a
double-blind randomised trial
an
infusion of
doxapram, 2 mg per min for 6 h immediately after surgery and repeated on the first postoperative day, or the same volume of saline, was given to 39 patients who underwent upper abdominal surgery and who were at high risk of postoperative pulmonary complications. The patients were assessed pre-operatively and during the first 5 postoperative days by physical examination, spirometry, blood-gas analysis, and chest radiography. Postoperative pulmonary complications for 2
were
defined
as
temperature
over
38°C
days, abnormal auscultation, pathological radiograph, and/or productive cough. Data from 16 patients per group were analysed. Significantly more patients in the placebo group had three criteria of postoperative pulmonary complication compared with the doxapram group (63% vs 19%). The doxapram group also had higher PaO2 postoperatively. Lancet 1990; 335: 936-38.
Introduction
Pulmonary complications are the most common cause of morbidity and mortality after surgical operations. The frequency after laparotomy varies from 5% to 80%, depending on the type of operation and the definitions used for pulmonary complications; most workers agree on a frequency around 20% for healthy individuals. Despite many advances in anaesthesia, the frequency has not changed much over the past 40 years.Z Controversy exists as to whether the respiratory stimulant doxapram can reduce pulmonary complications after surgery.3-S However, no reported study looked at high-risk patients. We have examined the effect of doxapram on postoperative pulmonary complications in such patients after upper abdominal surgery.
Patients and methods Patients 39 patients who were admitted for elective surgery involving the stomach, biliary tract, pancreas, colon, or kidney with incisions above the umbilicus and who fulfilled at least one of the following risk factors (lung disease with "functional dyspnoea" within the past 12 months, lung disease with cough and expectoration within the past 12 months, smoker of more than 15 cigarettes per day, occupational exposure to dust, or body weight exceeding 20% of median weight for height6) entered the trial. Patients with thyrotoxicosis, epilepsy, pregnancy, or dementia were excluded. Patients gave informed consent and the protocol was approved by the local ethical committee as being in accordance with the declaration of Helsinki II. Premedication consisted of hyoscine and morphine. Anaesthesia was standardised and balanced (thiopentone/pancuronium/fentanyl/droperidol or midazolam/nitrous oxide). General anaesthesia was combined with epidural analgesia with 0-5% bupivacaine in 16 patients via an epidural catheter, which was used when required for administration of morphine for postoperative analgesia. On arrival in the recovery room, the patients received either an infusion of doxapram, 2 mg per min in 500 ml isotonic saline for 6 h, or the same volume of saline over 6 h. The infusion was repeated during the afternoon of the first postoperative day. Allocation to the two groups was randomised and the two solutions were given double-blind. In the recovery room all patients received oxygen by nasal tube (2-4 ml per min). Chest physiotherapy was given twice daily from the first
postoperative day. Assessments
Physical examination, measurement of temperature and respiration frequency, and arterial blood-gas analysis were done
ADDRESSES: Department of General Surgery K, (J E. Jansen, MD, A I Sorensen, MD, A Pedersen, MD) and Department of Anaesthesiology (O Naesh, MD, C. J. Erichsen, MD), Frederiksberg
Hospital, University of Copenhagen, Denmark. Correspondence to
Dr J E Jansen,
Fuglsangpark 65, DK-3520 Farum, Denmark
937
TABLE I-PATIENTS’ CHARACTERISTICS TRIAL
No of patients
or
median
TABLE II-POSTOPERATIVE PULMONARY COMPLICATIONS
(range)
before the
operation and on each of the first 5 days after the operation. With the patient sitting forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1)’ and peak flow were measured on the day before the operation and on the first and third postoperative days with a dry spirometer (’Spirotron’, Drager). All measurements were made with the patients breathing room air. The first set of measurements was made 24 h after the operation before administration of doxapram or placebo. Chest radiographs in two planes were taken preoperatively and on the third postoperative day. The radiographs were analysed by a radiologist who was unaware of the treatment group. At the end of the study the presence of expectoration and the number of days in bed were recorded.
Postoperative pulmonary complications
were
defined
as
the
presence of one or more of the following criteria: (1) morning body temperature above 38.0°C for at least 2 days, with no suspicion of focus outside the lungs; (2) abnormal auscultation not heard
preoperatively; (3) productive cough atelectasis
or
or
infiltration. On clinical
purulent sputum; or (4) suspicion of pulmonary
embolism, lung-perfusion scintigraphy was done. Statistics
NS = not
significant
shown in table n: doxapram administration resulted in a significant reduction in many of the criteria. Similarly, when the combination of criteria was analysed, there was a significant reduction in those patients with up to three combinations. Postoperatively respiratory frequency was higher in the controls compared with the doxapram group, but this difference was significant on day 2 only. The results of arterial oxygen analysis are summarised in the figure. The mean Pa02 postoperatively was 9-4 kPa (SD 1-45) in the doxapram group compared with 8-5 kPa (1-45) in the In addition Pa02 at day 5 in those controls (p < 0°0001). patients receiving doxapram was not significantly different from the preoperative value whereas Pa02 on this day in control patients was significantly lower than the preoperative value (p 0-02). The mean arterial PaC02 values are shown in table ill. There were no differences in mean PaC02 or pH between the two groups. The respiratory function tests did not show significant differences between the two groups (table IV). The median duration of postoperative hospital stay was 9 days (range 5-22) in the doxapram group and 10 days (3-22) in the controls. 7 controls stayed for more than 10 days in the ward compared with 2 from the doxapram group (not =
Differences between the doxapram group and the control group were tested with Fisher’s exact test. Blood-gas analysis and spirometry were compared with unpaired t tests.
Results 16 patients who received doxapram and 16 who received placebo were analysed (table I). All findings related to the diagnosis of postoperative pulmonary complication are
significant). TABLE III-MEAN
(SE) ARTERIAL PaC02 (kPa) BEFORE AND AFTER OPERATION
*Slgnlflcant difference from TABLE IV-MEAN
Mean (SE) Pa02 preoperatively (P) and
days.
on
first 5
postoperative
mean
value before operation
(SE) FEV,
in same
group
(p < 0 05)
BEFORE AND AFTER OPERATION
938
3 patients additionally had pulmonary embolism, 1 in the doxapram group and 2 in the control group. 1 control patient died on day Iof massive pulmonary embolism. 7 patients were excluded from analysis. Doxapram infusions were discontinued in 3 patients; in 1 because of tachycardia and in 2 because of transient hypertension. "Control" infusions were stopped in 2 patients because of tachycardia and cardiac arrhythmias. 2 more patients were excluded: 1 in the doxapram group because of ventilator treatment before he had received any doxapram, and 1 control withdrew after the infusions were completed (excluded because of lack of data). The 3 patients from the doxapram group who were excluded received 800, 640, and 200 mg of doxapram, respectively. None showed any sign of postoperative pulmonary complications, while 2 of the 3 excluded control patients had fever, productive cough, and abnormal auscultation postoperatively. There is no available information about such complications in the third patient.
Discussion
Postoperative pulmonary complications are thought to be a consequence of hypoventilation leading to microatelectasis, veno-arterial shunting, and stasis of secretion, which predisopose to pulmonary infection and collapse of the lung. It has been suggested that doxapram, by acting as a "pharmacologic sigh" and inducing transient hyperventilation, can reduce this vicious circle.7 Doxapram increases both the tidal volume and the arterial oxygen tension in fit patients after abdominal surgery.4,5,8,9 Doxapram may also significantly reduce the frequency of cough and purulent sputum.5,8 However, several investigators have failed to demonstrate reduction in postoperative pulmonary complications when clinical and radiological examinations were taken into account. 10,12,13 The most important "high-risk" factors for postoperative pulmonary complications are chronic lung disease with dyspnoea and expectoration, smoking, obesity, immobility, age, duration of anaesthesia, and upper abdominal surgery or thoracic surgery.2,14 We studied high-risk patients: all underwent upper abdominal surgery, 47 % had chronic lung disease, 50% smoked more than 15 cigarettes daily, 53% were more than 20% overweight, and over half of the patients had more than one risk factor. The reduction in postoperative morbidity by doxapram was between 30 and 50% depending on which of the four criteria was used. Abnormal auscultation was the most sensitive tool in the diagnosis of postoperative pulmonary complications, as has been found before. 15 Taking temperature more than 38.0°C for 2 days, abnormal auscultation, and lung infiltration as criteria of postoperative pneumonia, 7 control patients had pneumonia compared with none in the doxapram group (p < 0.01). Despite the differences in postoperative pulmonary complications we found no significant difference in postoperative hospital stay (2 controls asked to be discharged at day 4 and 5, respectively, despite treatment for pneumonia, and 1 control died of pulmonary embolism on day 11). Our results are in broad agreement with an early study from Brazil in which doxapram significantly reduced postoperative atelectasis.11 Steele et al16 have shown that doxapram reduced postoperative pulmonary complications by 27% in patients who had normal respiratory indices and who underwent extensive abdominal operations. In both these studies, in contrast to others, doxapram was administered beyond the first 6 h postoperatively because
postoperative hypoxaemia can be protracted. In our study doxapram was administered by infusion immediately after surgery and on the first postoperative day. Taking postoperative pneumonia or combinations of up to three of our criteria of postoperative pulmonary complications into consideration, we found that the overall reduction in postoperative pulmonary morbidity produced by doxapram was 44% (20-70%). REFERENCES 1. Barlett RH. Pulmonary pathophysiology in surgical patients. Surg Clin North Am 1980; 60: 1323. 2. Garibaldi RA, Britt MR, Coleman ML, Reading JC, Pace NL. Risk factors for postoperative pneumonia. Am J Med 1981; 70: 677-80. 3. Anderson R, Krogh K. Post-operative analgesia combined with doxapram. Anaesthesia 1976; 31: 114. 4. Downing JW, Jeal DE, Allen PJ, Buley R. IV Doxapram hydrochloride and pulmonary complications after lower abdominal surgery. Br J Anaesth 1977; 49: 473-77. 5. Gawley TH, Dundee JW, Gupta PK, Jones CJ. Role of doxapram in reducing pulmonary complications after major surgery. Br Med J 1976; i: 122-24. 6. Natvig H. Nye Høyde-vekt-tabeller for norske kvinner og menn. Oslo: Landsforeningen for kosthold og helse, 1956. 7. Winnie AP, Gladisch JT, Angel JJ, Ramamurthy S, Collins VJ. Chemical respirogenesis II: reversal of postoperative hypoxemia with the "Pharmacologic Sigh". Anesth Analg 1971; 50: 1043-55. 8. Gupta PK, Dundee JW. The effect of an infusion of doxapram on morphine analgesia. Anaesthesia 1974; 29: 40-43. 9. Less NW, Howie HB, Mellon A, McKee AH, McDiarmid IA. The influence of doxapram on postoperative pulmonary function in patients undergoing upper abdominal surgery. Br J Anaesth 1976; 48: 1197-200. 10. Drummond GB, Park GR. Doxapram and postoperative chest complications. Anæsthesia 1983; 38: 3-6. 11. Plemont CB, Bibas RA, Campos RL, Guedes AHL. Prophylaxis of postoperative pulmonary atelectasis with Doxapram. Rev Brasil Anest 1970; 20: 1-14. 12. Hollway TE, Standford BJ. Effect of doxapram on postoperative oxygenation in obese patients. Anaesthesia 1982; 37: 718-21. 13. Sebel PS, Kershaw EJ, Rao WS. Effects of doxapram on postoperative pulmonary complications following thoracotomy. Br J Anæsth 1980; 52: 81-84. 14. Hechtman HB, Krausz MM, Utsonomiya T, Valeri CR. Preoperative assessment of high risk surgical patient. Surg Clin North Am 1980; 60: 1349-58. 15. Hansen G, Drabløs PA, Steinert R. Pulmonary complications, ventilation and blood gases after upper abdominal surgery. Acta Anæsth Scand 1977; 21: 211-15. 16. Steele RC, Walker WS, Irvine MKA. The use of doxapram in the prevention of postoperative pulmonary complications. Surg Gynecol Obstet 1982; 154: 510-12.
From The Lancet The case of Joseph Merrick at the London Hospital
Joseph Merrick, the so-called "Elephant man," died on Friday, the 11 th inst. He had been exhibited about the country for some time till the case attracted the attention of the authorities of the London Hospital, who offered him a shelter within their walls. It seems that on Thursday last the man was out in the garden apparently quite well. On Friday, at 1.30 pm, he was seen for the last time in his room alive, and at 3 pm he was discovered dead. Death was probably due to the falling back of the head, which was of enormous weight. Merrick has been the subject of many accounts, especially in American papers, and has been visited by half the celebrities in London. In 1886, as he was being exhibited in the East-end of London, he was seen by Mr Treves, who henceforward kept him under observation, and who has done much to contribute to the comfort of the unfortunate man. One of the greatest undertakings connected with the "Elephant man" was getting him into a theatre without his being discovered.
(19 April 1890)
