National Halothane Study: a Study of the Possible Association Between Halothane Anesthesia and Postoperative Hepatic Necrosis; Report. Edited by John P. Bunker [and Others] (1969) / Chapter Skim
Currently Skimming:
'REPORT ON HEPATIC NECROSIS'
'REPORT ON HEPATIC NECROSIS'
Pages 91-182
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 91... ...
It also includes discussion of some of the limitations of interpretation due to problems in the collection of necropsy data; tables relating such variables as operation, age, and institution to incidences of massive hepatic necrosis; and descriptions of special studies attempting to determine the etiology of massive hepatic necrosis. Subsequent chapters in Part III deal with interpretation in more detail, including the Pathology Panel's review of massive hepatic necrosis, the statistical analysis of hepatic data, and the clinical syndromes associated with postoperative hepatic necrosis.
|
From page 92... ...
These two groups represented the greatest loss of information in the study of massive hepatic necrosis. On the basis of clinical evidence, 13 of the nonnecropsied deaths were classified by the principal investigator as "probable massive hepatic necrosis" on the death abstraction form (Form m)
|
From page 93... ...
* Massive Hepatic Necrosis in Relation to Anesthetic Practice Observed occurrences of massive necrosis after all operations (Table 4)
|
From page 94... ...
Step 2 For cases thought to be massive hepatic necrosis, complete charts were sent to Data Collection Center. Slides or blocks of liver were 3ent to AFIP, Washington, D.C.
|
From page 95... ...
. TABLE 4. -- OBSERVED AND EXPECTED OCCURRENCE OF MASSIVE HEPATIC NECROSIS FOLLOWING HIGH-, MIDDLE-, AND LOW-DEATH-RATE OPERATIONS Operation Group Hal N-B Cyclo Ether Other Total Necrosis observed 2 0 1 0 0 3 Low -death-rate Necrosis expected*
|
From page 96... ...
Massive hepatic necrosis occurred more frequently after operations associated with high death rates: there were three cases of massive necrosis after 366,992 low-death-rate operations (or approximately 0.1 per 10,000) ; 47 after 427,355 middle-death-rate operations (1.1 per 10,000)
|
From page 97... ...
0) OF MASSIVE HEPATIC NECR 1-1 es originally selected b A because entries are mac rH r H rH rH rH CM in t^ OJ , -- ( 'xt rH i -- 1 r- 1 in 1 O CM in>fOrHrHrHr H O !
|
From page 98... ...
and high death rates. These factors undoubtedly contributed to the high rates of massive hepatic necrosis in the two institutions.
|
From page 99... ...
Alcoholism before death 1 67 U Hal Hal Unknown No Yea No 3 36 25 U Hal Hal Unknown No Yes No 5 44 64 V Hal Hal Yes No Ye s No 3 55 72 M No Hal Other Unknown No No No 2 68 42 U No Hal Other Unknown No Yes No 1 91 66 F Hal Hal Unknown No Yes No 8 93 63 U No Hal Cyclo Unknown No No No 3 97 67 M Hal Hal Yes No Yes No 9 99 21 U Hal Hal Unknown No No No 5 100 39 U Hal Hal Unknown No Yes No 10 122 58 r Hal Hal Unknown No Yes No 5 156 41 M No Hal Cyclo Unknown Unknown Unknown No 2 185 57 U No Hal Hal Unknown Yes Yes No 1 345 34 U No Hal Hal Yes No Yes No 7 616 81 U No Hal Other Unknown Yes •a No 3 636 55 M Hal Hal Unknown No No No 3 649 65 M No Hal Other Yes No No No 3 675 80 F No Hal Cyclo Unknown No No No 27 687 48 M No Hal N-B Unknown Bo XM No 4 691 64 M Hal Hal Unknown No No No 11 707 21 M No Hal Other Unknown No No No 3 709 37 r No Hal N-B Unknown Unknown No No 2 711 33 u No Hal Hal Unknown No No No 7 717 66 M No Hal Other Unknown No No No 2 719 62 F No Hal Cyclo Unknown No No No 8 TABLE 9. -- INCIDENCE AND RATES OF MASSIVE HEPATIC NECROSIS BY INSTITUTION AND ANESTHETIC PRACTICE Institution Halothane NB Cyclo Ether Other Total Rate of MHN/ 10,000 EA KA*
|
From page 100... ...
As an example of the unreliability of this classification, Table 10 lists five patients who suffered massive hepatic necrosis and who were evaluated preoperatively as physical status 1, i.e., "no complicating systemic disturbance." Of the five patients, three had severe debilitating disease for which they were to undergo definitive surgery, the fourth was 70 years old and had arteriosclerotic heart disease, and the fifth had a recent history of perforated duodenal ulcer. Clearly, none of these cases should have been classified as physical status 1.
|
From page 101... ...
septal defect, patent ductus Cyanotic on admission TABLE 11. -- INCIDENCE AND RATES OF MASSIVE HEPATIC NECROSIS BY PHYSICAL STATUS AND ANESTHETIC PRACTICE Physical Halothane N-B Cyclo Ether Other Total Rate/ EA*
|
From page 102... ...
Of the 26 patients in me halothane group who died from massive hepatic necrosis, 16 were jaundiced, whereas jaundice was recorded for only 15 of the 56 who had not received halothane. Possible explanations for this considerable excess in clinical jaundice in the halothane cases of massive hepatic necrosis include the following: (1)
|
From page 103... ...
TABLE 18 -- ETIOLOGY OF MASSIVE HEPATIC NECROSIS ASSESSED BT PATHOLOGY PANEL Number of pathologiats scoring*
|
From page 104... ...
* In most of the cases there appeared to be adequate clinical explanation for the massive hepatic necroses observed at necropsy: shock, especially with prolonged use of vasopressors; overwhelming infection; severe and prolonged congestive heart failure; and pre-existing hepatic disease.
|
From page 105... ...
TABLE 21 -- SUMJARY OF "UNEXPLAINED" CASES OF INTERMEDIATE HEPATIC NECROSIS Age, ^ years Anesthetic practice Contributing factor Total no.
|
From page 106... ...
IARY OF EXPLAINED CASES OF MASSIVE HEPATIC NECROSIS Case Anes. prac.
|
From page 107... ...
hal. 73 Hal 1 76 2 1,1 0 No No Yes 87 Hal 7 41 3 10,11,26 1 No Yes Yes 119 Hal 17 16 1 1 1 No No Yes 188 Hal 5 34 1 1 0 Yes No No 196 Hal 2 34 1 1 1 No No No 206 Hal 8 48 1 13 0 No Tea No 207 Hal 2 45 0 0 0 No No No 249 Hal 5 42 0 0 0 No No Yes 601 Hal 10 65 0 0 0 No No No 607 Hal 6 33 0 0 0 No No No 611 Hal 28 34 0 0 0 No Yes Yes 612 Hal 5 45 1 16 0 No No No 617 Hal 6 66 3 5,7,16 1 No No No 622 Hal 15 12 2 1,17 1 No No Yes 626 Hal 0 33 0 0 0 No No No 629 Hal 5 33 0 0 0 No No No 630 Hal 1 33 0 0 0 No No No 631 Hal 0 33 0 0 0 No No No 633 Hal 1 33 1 1 1 No Yes No 634 Hal 3 12 0 0 0 No No No 635 Hal 3 33 0 0 0 No No No 637 Hal 3 33 0 0 0 No No No 648 Hal 6 36 1 1 1 No No No 652 Hal 15 99 0 0 0 No No No 654 Hal 3 33 1 2 1 No No No 661 Hal 2 27 4 1,1,5,8 0 Mo No Yes 668 Hal 1 57 0 0 0 No No No 676 Hal 9 27 0 0 0 No No No 678 Hal 28 27 0 0 0 No No No 684 Hal 7 02 1 42 0 No No No 690 Hal 4 88 1 1 1 No No No 695 Hal 11 75 2 1,3 2 No No No 696 Hal 1 33 2 6,23 0 No Yee No 697 Hal 8 33 0 0 0 No No No 703 Hal 0 34 0 0 0 No Yes No 721 Hal 4 27 0 0 0 No No No 801 Hal 11 80 1 53 0 No No No 803 Hal 2 33 0 0 0 No Nr No 805 Hal 13 41 0 0 0 No Yes Yes 821 Hal 9 34 0 0 0 No Yes Yes 823 Hal 13 05 1 1 0 No No No 89 N-B 24 41 0 0 0 No Yes Yes 330 N-B 1 45 0 0 0 No Yea Yes 621 N-B 14 52 1 1 0 No No No 624 N-B 2 12 0 0 0 No No No 625 N-B 1 47 3 1,1,1 0 No No Yes 640 N-B 25 70 1 3 0 No No No 644 N-B 2 16 0 0 0 No No No 655 N-B 1 25 0 0 0 No Yes No 706 N-B 2 33 1 1 1 No No No 710 N-B 9 73 1 10 0 No No No 725 N-B 4 33 0 0 0 No No No 804 N-B 7 48 0 0 0 No No Yes 806 N-B 4 48 1 1 0 Yes No No 814 N-B 3 47 0 0 0 No No No 815 N-B 2 33 0 0 0 No Yes No 816 N-B 1 33 2 7,27 0 No Ye s No 7 Cyclo 12 50 0 0 0 No No No 34 Cyclo 19 59 0 0 0 No Yes Yes 92 Cyclo 5 33 2 17,17 0 No Yes Yes 112 Cyclo 5 44 1 1 1 No No Yes 134 Cyclo 13 33 0 0 0 No Yes Yes 200 Cyclo 5 60 0 0 0 No Yes No 107
|
From page 108... ...
220 Cyclo 6 45 1 24 0 No Yes Yes 224 Gyclo 8 20 0 0 0 Yea Yes Yes 248 Cyclo 2 44 0 0 0 Yea Yes Yes 268 Cyclo 2 44 0 0 0 No Yes Yes 308 Cyclo 3 44 0 0 0 No No Yes 344 Cyclo 2 47 0 0 0 No No No 348 Cyclo 2 44 0 0 0 No Yes Yes 366 Cyclo 2 45 0 0 0 No No No 608 Cyclo 23 52 3 2,7,9 0 Yes No No 615 Cyclo 10 88 1 14 0 No No No 671 Cyclo 4 57 0 0 c No No No 672 Cyclo 5 33 1 22 0 No No No 693 Cyclo 7 36 0 0 0 No No No 694 Cyclo 1 33 1 29 0 No No No 702 Cyclo 4 65 0 0 0 No Yes Yes 704 Cyclo 2 34 2 1,1 0 No No No 715 Cyclo 41 50 2 10,19 0 No Yes No 822 Cyclo 7 95 3 1,1,3 2 No Yes No 639 Ether 7 57 0 0 0 No No No 642 Ether 18 75 0 0 0 No No No 679 Ether 0 33 0 0 0 Yes Yes Yes 698 Ether 3 44 0 0 0 No Yes Yes 808 Ether 4 47 0 0 0 No No No 820 Ether 38 58 0 0 0 No No No 102 Other 1 44 0 0 0 No No No 190 Other 7 33 1 1 1 No No No 600 Other 2 42 1 9 1 No Yes Yes 604 Other 2 92 2 1,36 1 No No No 613 Other 2 57 1 1 0 No No No 614 Other 2 33 0 0 0 No Yes No 623 Other 2 33 0 0 0 No Yes No 627 Other 9 70 0 0 0 No No No 638 Other 1 44 0 0 0 No No No 659 Other 4 36 1 1 1 No No No 663 Other 1 22 2 1,1 0 No No No 674 Other 12 88 1 2 0 No No No 683 Other 33 27 0 0 0 No No No 699 Other 4 44 0 0 0 No No No 722 Other 32 12 0 0 0 No No No 818 Other 5 40 0 0 0 No No No 108
|
From page 109... ...
Lobular polymorphonuclear cytosis was the only significant variable oriented with "no halothane." Many of the cases selected preferentially by this analysis did, in fact, involve halothane, and most of these are the unexplained cases of massive hepatic necrosis. The inherent weakness of this analysis is that, when the number of factors (53)
|
From page 110... ...
Blood pressure was 140/90. Clinical Course: One day after admission to the hospital, he had bronchoscopy under local anesthesia, which showed an irregularity of the orifice of the left upper lobe; this area was biopsied and •Anesthetic agent not included in these summaries to allow unbiased clinical and pathologic review.
|
From page 111... ...
Physical Examination: He was well developed and well nourished and had no abdominal mass, tenderness, or jaundice. Blood pressure was 140/75.
|
From page 112... ...
Blood pressure was 170/80. Clinical Course: One day after admission to the hospital she underwent cholecystectomy and liver biopsy.
|
From page 113... ...
Physical Examination: She was pale but not jaundiced. Blood pressure was 110/60.
|
From page 114... ...
Blood pressure was 120/80. There was moderate right upper quadrant tenderness, but no definite mass.
|
From page 115... ...
Blood pressure was 110/80. There was no jaundice or abdominal mass or tenderness.
|
From page 116... ...
Physical Examination: She was obese, had a palpable tumor in the left breast, had an umbilical hernia, was not jaundiced, had no abdominal mass or tenderness, and had a blood pressure of 160/90. Clinical Course: X-rays confirmed the presence of gallstones and a hiatus hernia.
|
From page 117... ...
SUMMARY OF CASE 135 History: This 56-year-old white woman entered the hospital as an emergency because of acute pain in the right lower extremity. She had been well until 24 hr before the final admission, when she developed severe pain in the right shoulder and chest.
|
From page 118... ...
Details of blood pressure, urine volume, and the presence or absence of jaundice are not available. The chronologic relationships of surgery to death are not known, except for the fact that he died 3 days after the first operation.
|
From page 119... ...
He had been in the hospital for 3 days, 4 months before, when cardiac catheterization performed under local anesthesia showed findings compatible with aortic stenosis. Laboratory findings at that time were: hemoglobin, 13.8; PVC, 46.5; WBC, 10,500; urinalysis, normal; BUN, 16; sodium, 139; potassium, 4.5; chloride, 104; CO2 combining power, 31; calcium, 10.8; phosphorus, 3.7; alkaline phosphatase, 2.2; bilirubin, total 1.4, direct 0.4, and indirect 1.3; BSP retention, 0; prothrombin time, 100 percent; and transaminase, 14.
|
From page 120... ...
Three months before the final hospital admission, he underwent right heart catheterization, and special x-ray studies under local anesthesia showed dilatation of the aortic ring. He had no history of congestive heart failure.
|
From page 121... ...
Physical Examination: She was severely ill, slightly jaundiced, vomiting, and disoriented. Temperature was 39 C, pulse 112, and blood pressure 100/70.
|
From page 122... ...
Clinical Course: Two days after admission, she underwent a procedure for closure of an interventricular septal defect, resection of infundibular stenosis, and tracheostomy under total cardiopulmonary bypass on a heart-lung machine with hypothermia. She tolerated this procedure and was doing well until the 8th day, when she abruptly became febrile and hypotensive, and was thought to have pulmonary embolism or septicemia.
|
From page 123... ...
The abdomen was markedly distended with ascites; there was vague right upper quadrant tenderness, but no mass. Blood pressure was 120/70.
|
From page 124... ...
Two months before the final hospitalization, she had been admitted for 2 days for cardiac catheterization, which had shown findings of an interatrial septal defect. She had received penicillin and other injections at that time.
|
From page 125... ...
Clinical Course: She was thought to have ventricular septal defect with left-to-right shunt and pulmonary hypertension. One day after admission, she underwent a complex cardiac operation with total cardiopulmonary bypass on a heart-lung machine, and was found to have a very unusual condition involving a patent ductus arteriosus, a congenital deformity of the mitral valve, an extremely large interventricular septal defect, anomalous tricuspid valves, and severe pulmonary hypertension.
|
From page 126... ...
Nineteen months before final hospitalization, cardiac catheterization was performed elsewhere, and she was found to have a ventricular septal defect, patent ductus arteriosus, patent foramen ovale, and pulmonary hypertension with bidirectional shunt. A procedure for closure of the patent ductus arteriosus was performed under general anesthesia 1 year before the final hospital admission.
|
From page 127... ...
Clinical Course: He was treated medically for his chronic congestive heart failure, but continued to have chest pain, hemoptysis, and dyspnea even at rest, and developed friction rubs over both lungs. He gradually deteriorated.
|
From page 128... ...
Some 14 months before the final admission, he developed a left pneumothorax and was found to have malignant cells in his pleural fluid. Six weeks before final hospital admission, a retrocardiac mass was found on x-ray.
|
From page 129... ...
Six years before the final admission, she underwent cardiac catheterization elsewhere, showing a ventricular septal defect with a leftto-right shunt and pulmonary hypertension. One month before the final hospital admission, cardiac catheterization under local anesthesia was performed.
|
From page 130... ...
A diagnosis of mitral insufficiency and right-sided cardiac failure was made. In the year before the final admission, hospitalization was necessary for several episodes of severe congestive heart failure.
|
From page 131... ...
Some 15 months before the final admission, tachycardia developed and atrial fibrillation was found. Some 12 months before the final hospital admission, she had open-heart surgery at another hospital, where she allegedly had an "open and shut" operation.
|
From page 132... ...
Clinical Course: She was thought to have rheumatic heart disease with congestive heart failure and mitral insufficiency, tricuspid stenosis, tricuspid insufficiency, aortic stenosis, and cardiac cirrhosis, or chronic hepatitis. Five days after admission, plastic reconstruction of the tricuspid and mitral valves was performed, with total cardiopulmonary bypass on a heart-lung machine with intentional hypothermia.
|
From page 133... ...
Clinical Course: Rheumatic heart disease was diagnosed, with mitral stenosis, aortic insufficiency, atrial fibrillation, and congestive heart failure, compensated. Six days after admission, she underwent surgery for a mitral valvulotomy and then suturing of the mitral valve, with total cardiopulmonary bypass on a heart-lung machine with hypothermia, and a tracheostomy.
|
From page 134... ...
For 1 month, enlarged nontender inguinal lymph nodes were noticed; although no diagnosis had been made, he underwent examinations and numerous blood tests on an out-patient basis. Some 2 weeks before the final admission, he developed fever to 103 F, abdominal pain and distention, loss of appetite, and a 15-lb weight loss, and was hospitalized elsewhere, found to have ascites, and had paracentesis at least once, producing 4 liters of fluid.
|
From page 135... ...
SUMMARY OF CASE 673 History: This 68-year-old white woman entered the hospital for the eighth time because of weight loss, loss of appetite, and abdominal pain. Five years before the final admission, a right radical axillary lymph node dissection was done for adenocarcinoma originating in the axillary sweat glands.
|
From page 136... ...
Blood pressure was 180/105. There were signs of cardiac enlargement.
|
From page 137... ...
Physical Examination: He was emaciated, dehydrated, and chronically ill, but not jaundiced. Blood pressure was 170/100.
|
From page 138... ...
His ulcer symptoms had been very severe for 2 weeks before the final hospital admission; he had vomited blood once and had lost 20 Ib. He had been hospitalized elsewhere 10 days before the final admission.
|
From page 139... ...
Blood pressure was 140/40. There were decreased breath sounds and rales over the left lower lobe.
|
From page 140... ...
The underlying cause of this was never determined and the condition cleared with a tube thoracostomy. Seventeen years before the final admission, he had been known to have a duodenal ulcer manifested by abdominal pain.
|
From page 141... ...
These symptoms had been gradually increasing in severity. Six months before the final hospitalization, he was admitted for cardiac catheterization, which yielded the diagnosis of interventricular septal defect with infundibular pulmonary stenosis.
|
From page 142... ...
On her final admission for elective cardiac surgery, she had had no progression of symptoms, nor any history of congestive heart failure.
|
From page 143... ...
Clinical Course: Cardiac catheterization with angiocardiography was done under local anesthesia, giving the findings of interventricular septal defect, bidirectional shunt, valvular and infundibular pulmonic stenosis, anomalous right upper pulmonary venous drainage into the superior vena cava, and a patent foramen ovale or an interatrial septal defect. A patent ductus arteriosus was not demonstrated.
|
From page 144... ...
Arteriosclerotic heart disease was prevalent for 5 years. Five years before the final admission, he had had a myocardial infarction, and he had been on digitalis since then.
|
From page 145... ...
, appeared chronically ill, and was not jaundiced. Blood pressure was 120/70.
|
From page 146... ...
Blood pressure was 100/70. There was bilateral gynecomastia.
|
From page 147... ...
There were systolic and diastolic heart murmurs and signs of cardiac enlargement and atrial fibrillation; there was no abdominal mass or tenderness, and no sign of congestive heart failure. Clinical Course: Seven days after admission, she underwent a procedure for valvulotomy and plastic correction of the insufficiency of the mitral valve with a Teflon patch, including total cardiopulmonary bypass on a heart-lung machine.
|
From page 148... ...
5, indirect 0.3; and BSP retention, less than 5 percent. One year before the final admission, he was admitted for the second time for 21 days with severe pneumonia of the left lower lobe and left upper lobe, plus congestive heart failure.
|
From page 149... ...
Four years before the final admission, she had had cardiac catheterization, which showed interventricular septal defect and pulmonic stenosis. The liver was not palpable at this admission.
|
From page 150... ...
Congenital heart disease with pulmonary stenosis, valvular and infundibular; interventricular septal defect, membranous, high, large, anterior; bicuspid pulmonary valve; right ventricular hypertrophy; operated, with significant right ventricular outflow tract obstruction, unintended, entrapment of the chordae tendinae of the tricuspid valve in the sutures for the repair of the interventricular septal defect, and significant incomplete closure of the interventricular septal defect.
|
From page 151... ...
reviewed the files of the cases necropsied at his institution during the 4-year period of the Study and selected all those thought to reflect massive hepatic necrosis that occurred within 6 weeks of the administration of a general anesthetic. This survey yielded a total of 184 cases from all institutions; these were gathered from an over-all total of 10,171 complete necropsies.
|
From page 152... ...
Most of the remainder represented minimal necrosis and were therefore excluded. The final tally, therefore, combining both the initial screening and the supplementary selection, was 82 cases of massive hepatic necrosis and 115 cases of intermediate hepatic necrosis.
|
From page 153... ...
A rare necrotic cell, sequestered from its neighbors, assumed a hyaline appearance reminiscent of the acidophilic body observed in viral hepatitis (6,11,15)
|
From page 154... ...
6.) Figure 6. -- Massive necrosis (Case 206)
|
From page 155... ...
X 200 Figure 8. -- Massive necrosis, periportal area (Case 36)
|
From page 156... ...
. It seems most unlikely that instances of truly massive hepatic necrosis would escape the screening methods used among the necropsy cases.
|
From page 157... ...
X200 least one case, misinterpreted as an abnormality and bears comment only because it was taken as an indication of intrinsic hepatic injury. The accumulation of parenchymal fat was also considered by some as evidence of hepatic damage.
|
From page 158... ...
Each of these conditions exhibited distinguishing features, and the Pathology Panel felt justified in their exclusion from consideration. Indeed, in almost every instance the manner of death was unrelated to hepatic failure and reflected, instead, another primary disorder.
|
From page 159... ...
^y. 'Tgl -A^98,Vz Figure 18. -- Massive necrosis (Case 36)
|
From page 160... ...
Despite this, it is believed that all examples of massive hepatic necrosis and almost all those with intermediate necrosis among cases necropsied were brought to light. A scrutiny of necropsy diagnoses by varied means led to the accumulation of 972 cases of possible hepatic necrosis; microscopic sections of 946 of the livers were procured for review.
|
From page 161... ...
Carriers of hepatitis virus in the blood and viral hepatitis in whole blood recipients.
|
From page 162... ...
Thus, suspicion of hepatic injury cannot be relied on either to identify the majority of possible cases or to ensure necropsy. Some appraisal of the incidence of massive hepatic necrosis in the nonnecropsied deaths can be obtained by comparing the rate of massive hepatic necrosis per necropsy in institutions with high necropsy rates with that observed in institutions with low necropsy rates.
|
From page 163... ...
-X45 50 55 60 65 70 75 PERCENT NECROPSIES IMPLICATIONS OF THE MISSING CASES AND THE POSSIBILITY OF NECROPSY BIAS The conclusion that a substantial portion of the massive hepatic necrosis cases was not identified is disturbing, because some of the factors determining whether a case was necropsied are related to those being studied. For example, if hepatic failure and death occurred in a patient who had received halothane, already under some suspicion during the years studied, necropsy might have been more likely to be performed.
|
From page 164... ...
254.9 218.2 147.4 102.0 134.0 856.5 Rates/1000 deaths 5.35 4.56 6.50 3.58 3.19 4.87 Rates 10,000 EA 1.02 0.69 1.70 0.49 0.82 0.96 TABLE 1. -- OBSERVED AND EXPECTED OCCURRENCE OF MASSIVE HEPATIC NECROSIS FOLLOWING HIGH-, MIDDLE-, AND LOW-DEATH-RATE OPERATIONS * Necrosis expected (H)
|
From page 165... ...
THE "UNEXPLAINED" CASES Seven of the nine patients with "unexplained" massive hepatic necrosis had received halothane during the final operative procedure. Five of the seven died after clinically evident hepatic failure; this was in contrast with the patients whose massive necrosis was considered explained by prolonged shock or overwhelming sepsis, and in most of whom hepatic failure was not suspected clinically.
|
From page 166... ...
Cases involving lesser degrees of necrosis were submitted only as possible massive necrosis, and there was evidence that a doubtful case was more likely to be submitted if halothane had been the anesthetic agent. An example of this bias is provided by the distribution of anesthetic agents among the cases of missing data.
|
From page 167... ...
MHN per 100 deaths MHN's/ deaths Institution H N-B 3 E 0 1 1.1 189 55 7 5 38 0.7 2/294 2 226 94 1.1 177 22 95 0.3 2/614 3 25 106 20 1 49 0/201 4 105 98 1.3 223 94 197 0.4 3/717 5 333 267 0.9 346 55 196 0.2 3/1197 6 90 103 23 56 1.7 60 0.4 1/332 7 152 45 98 58 189 0/542 8 0.4 671 0.9 115 2.0 51 0.3 299 1.9 212 0.6 8/1348 9 0.8 261 0.4 256 0.8 121 235 103 0.4 4/976 10 0.8 228 1.3 152 1.0 295 2.4 42 82 0.9 7/799 n 128 2.8 71 1.2 84 122 0.7 150 0.7 4/555 12 0.6 178 30 1.2 173 7 116 0.6 3/504 13 71 12 98 2 63 0/246 u 28 11 56 6 40 0/141 15 64 129 1.1 190 1.6 61 142 0.5 3/586 16 67 0.4 253 81 3 115 0.2 1/519 17 52 8 19 18 2.2 89 1.1 2/186 18 73 75 0.8 124 10 45 0.3 1/327 19 0.4 228 80 97 2 79 0.2 1/486 20 2.3 43 41 0.8 245 0.8 131 0.4 267 0.7 5/727 21 0.8 248 1.6 185 0.5 185 20 0.9 177 0.9 7/815 22 1.6 243 2.2 92 138 8 133 1.0 6/614 23 18 40 19 0 6 0/83 24 2.0 147 0.6 514 0.4 229 3.7 27 1.7 118 1.0 10/1035 25 126 50 166 23 0.5 213 0.2 1/578 26 125 131 78 10 48 0/392 27 98 30 113 6 49 0/296 28 10 5 022 0/19 29 2.2 89 15 35 2 30 1.3 2/171 30 2.3 130 47 7.7 26 0 20 2.2 5/223 31 59 23 79 1 18 0/180 32 137 1 4 68 0 57 0/276 33 0.5 210 140 106 63 162 0.1 1/681 34 11 5 75 5 84 0/180 TOTAL DEATHS 4863 3292 3845 1396 3444 167
|
From page 168... ...
It is of interest here that such differences do not seem to manifest themselves in the massive hepatic necrosis rates. Table 4 shows the rate of massive hepatic necrosis per 100 deaths by institution and by anesthetic.
|
From page 169... ...
Particular attention was paid to the presence of shock and heart failure, and their relationship to any clinical evidence of hepatic disease that developed during a patient's illness. Cases were selected solely on the basis of postmortem hepatic histology, so that it was possible that a patient might have histologic massive hepatic necrosis without having displayed any symptoms of hepatic disease during life; in fact, that proved to be the most common situation.
|
From page 170... ...
: Exploratory Vagotomy and pyloroplasty Gastrectomy Colectomy Enteroenterostomy Gastroenterostomy and choledochojejunostomy Whipple procedure Portacaval shunt Cholecystectomy Cardiac surgery on bypass Repair of aneurysm 11 2 5 1 1 1 1 1 2 19 5 Miscellaneous (16) : Clip aneurysm of internal carotid artery 1 Removal of celestin tube 1 Exploration right common iliac artery l Aortofemoral graft 1 Inferior vena cava ligation 1 Saddle embolectomy aorta 1 Sympathectomy and pericardial poudrage 1 Thoracotomy for hemostasis 1 Above-knee amputation 1 Pneumonectomy 1 Operation not directly associated with event leading to 6 hepatic necrosis (5 deaths from sepsis and 1 from cerebrovascular thrombosis)
|
From page 171... ...
Jaundice tnetic Shock 1 Noted to be Jaundiced on day he died 1 Hal 44 Jaundiced last day of life 1 3 Hal 74 History of hepatic disease 9 1 Cyclo 185 Jaundiced last day 1 2 Hal 222 Congestive failure due to aortic stenosis 5 5 N-B 234 Congestive failure; postoperative dissecting aneuiysm 9 10 N-B of aorta 345 Alcoholism; hemolytic crisis 3 days before death 1 2 Hal 687 Peritonitis; thrombosis iliac artery 2 1 N-B 712 Atrial septal defect; pulmonic stenosis* 2 4 N-B 716 Jaundiced 2 1 Hal 802 Cirrhosis with bleeding varices 1 2 Cyclo 352 Jaundiced before death 2 hr 1 363 Carcinoma head of pancreas with liver metastases, On admisbiliary tract obstruction, and ascending cholangitis sion 605 Carcinoma stomach; biliary tract obstruction from On admismetastasis; bleeding gastric ulcer sion 650 Carcinoma esophagus; lung abscess 16 658 Rheumatic mitral stenosis, mitral insufficiency, and On admistricuspid insufficiency*
|
From page 172... ...
Cases 98 and 99 never developed jaundice, but were placed in the hepatitis group because they died with normal cardiovascular systems and had hepatic necrosis at necropsy (anicteric massive hepatic necrosis due to viral hepatitis has been previously reported)
|
From page 173... ...
-- CLINICAL FEATURES OF PATIENTS IN THE HEPATITIS CATEGORY* Onset of event, days after last operation CNS symptoms Remarks Case Operation Jaundice Fever Bleeding Death PreComa coma 36 Many dressing changes On admission 2 and skin grafts (total, 9 operations)
|
From page 174... ...
TABLE 7. -- TREATMENTS RECEIVED BY THE PATIENTS IN THE HEPATITIS CATEGORY THAT MAY HAVE BEEN ETIOLOGICALLY RELATED TO MASSIVE HEPATIC NECROSIS No. of transfusions 10 or more days before Jaundice Drugs reported to cause Jaundice Principal anesthetic (last operation)
|
From page 175... ...
who developed postoperative massive hepatic necrosis of the hepatitis type received halothane for their final operation, whereas the over-all incidence of halothane anesthesia in the entire series of over 800,000 patients was 29.8 percent. Similarly, the percentage of patients who received multiple administrations of halothane was considerably higher among the hepatitis group (six of 15)
|
From page 176... ...
Fatal hepatic necrosis secondary to isoniazid therapy.
|
From page 177... ...
An estimated 27,677 patients underwent cholecystectomy, common-duct exploration, or both, with or without other major surgery, and massive hepatic necrosis occurred in only six of them, for a rate somewhat lower than those for most other abdominal operations. One of the six patients had received halothane, whereas halothane was administered for approximately 30 percent of *
|
From page 178... ...
. There usually appeared to be an adequate clinical explanation for the massive hepatic necrosis observed at necropsy, shock, especially with prolonged use of vasopressors; overwhelming infection; severe and prolonged congestive heart failure; and pre-existing hepatic disease.
|
From page 179... ...
The data of the Study also allow us confidently to disclaim any special risk of fatal hepatic injury from halothane in patients undergoing biliary tract surgery, some of whom can be assumed to have suffered some degree of preoperative hepatic damage. The Study did not attempt to collect data on preoperative hepatic disease, except for the 82 cases finally identified as massive hepatic necrosis, and therefore relatively little can be said about the risk of halothane in patients known preoperatively to suffer from diseases of the liver.
|
From page 180... ...
Cyclopropane was followed by a greater incidence of massive hepatic necrosis than any of the other anesthetics. Inasmuch as all but one of the 25 cases of massive necrosis that followed administration of cyclopropane were classified as "explained," there is reason to believe that the disproportionately large total number might well have been related to the selective use of cyclopropane for patients in shock; but the possibility that cyclopropane damages the liver cannot be excluded.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.