Acute pancreatitis: demographics, aetiological factors and outcomes in a regional hospital in South Africa.
Abstract: Introduction. The spectrum of aetiologies and outcomes of acute pancreatitis in South African settings is under-reported. We report our experience at a regional hospital and compare it with international norms.

Patients and methods. Data were prospectively collected on all admissions of patients with acute pancreatitis to a regional hospital during the period June 2001-April 2006. The causes of the pancreatitis were noted and complications and mortality rate were determined.

Results. From June 2001 to April 2006 there were 322 admissions of 282 patients with acute pancreatitis. The median age was 37 years (range 13-73 years). There were 94 females and 188 males. Episodes of pancreatitis were associated with alcohol consumption in 62% of cases and with gallstones in 14%; 4% of cases were associated with both gallstones and alcohol consumption, 8% with dyslipidaemia and 5% with retroviral disease. In 15% of admissions local complications developed, and 9% of admissions ended in death of the patient. Of the 28 deaths, 71% occurred in the first 2 weeks.

Conclusions. As in other South African reports, alcohol was the main cause of pancreatitis. Outcomes in this series are similar to those in Western studies except that the majority of deaths occurred early, implying that improved supportive care may improve overall survival.
Article Type: Report
Subject: Pancreatitis (Risk factors)
Pancreatitis (Diagnosis)
Pancreatitis (Care and treatment)
Pancreatitis (Demographic aspects)
Pancreatitis (Patient outcomes)
CT imaging (Usage)
CT imaging (Health aspects)
Authors: Anderson, F.
Thomson, S.R.
Clarke, D.L.
Loots, E.
Pub Date: 08/01/2008
Publication: Name: South African Journal of Surgery Publisher: South African Medical Association Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2008 South African Medical Association ISSN: 0038-2361
Issue: Date: August, 2008 Source Volume: 46 Source Issue: 3
Geographic: Geographic Scope: South Africa Geographic Code: 6SOUT South Africa
Accession Number: 204550612
Full Text: Although acute pancreatitis is a common reason for emergency hospital admissions, (1) there is a paucity of information about the disease in a South African context (2,3) and to what extent disease severity and outcomes compare with published literature on the subject.

We prospectively investigated the hospital prevalence, aetiology, disease severity and outcomes of pancreatitis in a regional hospital setting in Durban, South Africa.

Patients and methods

During the period June 2001-April 2006 data were prospectively collected on all admissions of patients to Addington Hospital with a diagnosis of pancreatitis.

The diagnosis was established by clinical presentation, together with an elevated serum amylase level (at least twice the upper limit of normal4) or an elevated urine amylase level >760 U/l. (4) Imaging by ultrasound or computed tomography scan was used as a confirmatory or primary diagnostic investigation where indicated. The pancreatitis was considered to be idiopathic when a cause was not apparent after initial screening.

All patients were assessed using the Glasgow criteria. (5) Organ dysfunction (Atlanta criteria) (6) was evidenced by the presence of shock (systolic blood pressure <90 mmHg), pulmonary dysfunction (Pa[O.sub.2] <60 mmHg), renal failure (creatinine level >174 [micro]mol/l) or gastrointestinal bleeding (>500 ml/h). A CT scan was an additional diagnostic modality in patients judged to have severe disease, to diagnose and quantify pancreatic necrosis. (7,8) Lipid assays were performed routinely.

Patients with pancreatic necrosis and requiring organ support were given ciprofloxacin.

The number of patients requiring intensive care unit admission, the duration of ICU and hospital stay, the development of complications and the number of deaths were noted.

Statistical analysis

Descriptive statistics were used to determine the characteristics of the cohort. These were stated as mean values and range.

Results

From June 2001 to May 2006, there were 322 admissions (1% of total admissions to the general surgical wards in the same period) of 282 patients with a diagnosis of acute pancreatitis, of whom 94 were female and 188 male. The median age of the patients was 37 years (range 13-73 years) and the median hospital stay was 6 days (range 1-123 days).

The median serum amylase level was 676 U/l (range 25-11 144 U/l), and the amylase level reached the diagnostic cutoff level in 252 admissions (78%). In 53 admissions (16%) an elevated urine amylase level supported the diagnosis where the serum amylase was normal or marginally elevated. In 6 patients with markedly elevated triglycerides and normal or unmeasurable serum or urine amylase the clinical presentation and the lipaemia were considered supportive of the diagnosis.

In 4 patients the diagnosis was established at laparotomy. In 2 patients with an elevated amylase level ischaemic bowel was suspected, but in the other 2 the diagnosis was not suspected preoperatively. Ultrasound and CT scan were the sole confirmatory investigations in 7 cases. The aetiological associations are set out in Table I. Alcohol and gallstones were the main factors associated with pancreatitis. Sixteen patients were known to have HIV infection. One of these had a possible alcohol association, and in 8 patients on antiretroviral therapy with didanosine and stavudine these drugs were thought to be responsible for the pancreatitis. In the remainder the cause was uncertain. Primary hyperparathyroidism and hereditary spherocytosis accounted for a single case each.

Of the 44 patients with gallstone-related pancreatitis and the 14 with gallstones and alcohol consumption as probable causes, 42 had cholecystectomy within 30 days of the the admission, 2 refused surgery and 1 had had a previous cholecystectomy. The others did not honour appointments for cholecystectomy at 6 weeks. Seventeen had endoscopic retrograde cholangiopancreatography, 14 for jaundice, 2 for persistent symptoms and 1, who had proven choledocholithiasis, during advanced pregnancy. Five patients with pancreatitis associated with gallstones and no jaundice died. ERCP was not performed in any of these patients.

Complete assessment using a modified Glasgow Score of 8 criteria was done in 301 of the 322 admissions (93%). The proportions of patients assessed as having severe disease according to the Glasgow criteria and the organ failure criteria of disease severity were similar (Table II).

Of the patients 34 (11%) were admitted to the intensive care unit; 21 of them died, in all of whom the Glasgow criteria had predicted severe disease. The range of stay in the ICU was 1-23 days. Seven patients died without ICU admission. The Glasgow criteria had predicted mild disease in 5 of these patients and severe disease in 2. Unfortunately a bed in the ICU was not available in the latter 2 cases.

Thirty-three (32%) of the 102 patients who had CT scan assessment had pancreatic necrosis. One was managed with percutaneous drainage and another with open surgery and lavage. In the other 31 management was expectant as infection of pancreatic necrosis was not established. Ten of these patients developed pseudocysts, 4 a pancreatic abscess and 7 died.

Forty-nine patients (15%) developed local complications. Pseudocysts occurred in 29 (9%). Ten had spontaneous resolution, 7 were managed expectantly and 7 were lost to follow-up. Four were drained by endoscopic means and 1 had spontaneous drainage into the duodenum.

Four patients (1%) developed an abscess. Two were successfully treated by percutaneous drainage and open drainage with lavage, but in the other 2 percutaneous drainage resulted in colonic fistula and subsequent death.

Transient obstructive jaundice (21 cases, 7%), gastric outlet obstruction (10, 3%) and haemorrhage (3, 1%) resolved with supportive therapy. Portal hypertension developed in 1 case (0.3%) as a consequence of portal vein thrombosis and a pseudocyst in the region of the head of the pancreas. This resolved after transduodenal endoscopic cyst drainage.

There were 28 deaths, of which 71% occurred within 2 weeks. Assessment of severity using the Glasgow Score and organ failure severity assessment score predicted mild disease in 11 of the deaths. The distribution of the deaths according to aetiology is set out in Table I. Dyslipidaemia and a dual aetiology of alcohol and gallstones were associated with the highest proportions of deaths.

Discussion

Internationally the incidence of pancreatitis is rising. In 1987 there were 108 000 admissions in the USA (excluding Veterans Affairs hospitals), with 2 251 deaths. (9) More recently in a 2006 report this had more than doubled to 220 000 admissions. (10) In the UK a rising incidence by a factor of 10 has been noted from the 1960s to the 1980s, but there is still a wide regional variation from 150 to 420 cases per million population.1,11,12 In South Africa there have been no incidence studies and only 2 hospital prevalence studies. (2,3)

In this cohort alcohol was implicated in two-thirds of the admissions and gallstones in 17%, while 5% were deemed idiopathic (Table I). These proportions are similar to those in the Cape Town (2) and Johannesburg (3) series. Table II shows the variation in the aetiologies of acute pancreatitis in US, European and South African settings. In general, Western cohorts have a significantly higher prevalence of gallstone aetiology.

Patients were not routinely counselled for HIV testing, so only those with known disease were identified. Pancreatitis in patients infected with HIV is most frequently associated with antiretroviral medication and with opportunistic pancreatic infections. (13-16) In this series over half the patients were receiving treatment but none were identified with pancreatic infection. Outcomes have been found to be similar to non-HIV-related pancreatitis, (16) and our limited data support this observation. However, pancreatitis has been shown to be associated with an increasing proportion of deaths in patients on highly active antiretroviral therapy (HAART). (17) HAART has been associated with the development of pancreatitis. The antiretroviral drug most frequently associated with pancreatitis is didanosine, an adenosine analogue. (13,15) Ritonavir, a protease inhibitor, has been associated with severe hypertriglyceridaemia and pancreatitis. (18) Pentamidine, an aromatic diamidine used in the treatment and prophylaxis of Pneumocystis carinii pneumonia, also causes pancreatitis by a direct toxic effect. (13)

In view of the over 30% prevalence of HIV in surgical patients in our region (19) it is important that details of HAART therapy are obtained. HAART can then be modified to reduce the risk of subsequent pancreatitis.

Hypercalcaemia is rare, as our single case illustrates, but worth investigating because although primary hyperparathyroidism is identified in less than 1 in 400 cases, treatment will be curative for both conditions. (20)

In the diagnostic work-up of acute pancreatitis an elevated amylase level is nonspecific as it may be raised in a number of acute abdominal conditions. Thomson et al. (12) performed laparotomies in 7 patients (2%) because of diagnostic doubt. In the present series laparotomy confirmed the diagnosis in 4 cases (1%), ultrasound in 4 (1%) and CT scan in 3 (1%).

Of Thomson et al.'s series of 378 patients (12) 26 (7%) developed pseudocysts and 11 (3%) pancreatic abscesses, figures similar to the present series, in which we found 29 (9%) pseudocysts and 4 (1%) pancreatic abscesses.

Mortality

The ability of the Glasgow Score and organ failure severity assessment score to predict severe disease in a number of series is set out in Table II. Figures for the Glasgow Score in the different studies are similar. The specificity is generally in the upper 80s, but sensitivity, i.e. the ability to detect all those with severe disease, is much lower. It was disappointing that the organ failure severity assessment score did not improve on the sensitivity. These indices are ineffective as clinical management tools because they do not accurately select patients for monitoring in a high-care unit. They are more useful for epidemiological comparison.

The mortality rate of 9% in this series is comparable to the mortality reported in some of the cited references. (21-23) Thomson et al.12 reported a mortality of 15%, although only half of the deaths were thought to be directly related to complications of pancreatitis. The mortality due to gallstones at 9% is comparable to another series, which showed a mortality rate of 6%. (23)

The proportions of early and late deaths (with 2 weeks as the cut-off point) in different series are set out in Table III. A larger proportion of patients in this series died early, from systemic inflammatory response syndrome and multiple organ dysfunction syndrome, than in almost any other series. It is interesting to note that 7 of the patients who died early were not admitted to the ICU for monitoring. This again illustrates lack of an effective tool with which to predict the need for ICU admission.

Conclusion

This series reaffirms that alcohol is the major factor associated with acute pancreatitis in the South African context. It needs to be kept in mind that both HIV and HAART are possible aetiological factors, as the latter can be altered to reduce the risk. Severity indices are poor practical management tools owing to their low sensitivity. The mortality rate is similar to norms elsewhere, but the majority of deaths occur in the first 2 weeks. Improved selection for and availability of early supportive management have the potential to reduce mortality.

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F. ANDERSON, M. MED., F.C.S. (S.A.)

S. R. THOMSON, CH.M., F.R.C.S.

D. L. CLARKE, M.MED.SCI., F.C.S. (S.A.)

E. LOOTS, F.C.S. (S.A.)

Department of Surgery, Addington Hospital and Nelson R Mandela School of Medicine, University of Kwa-Zulu-Natal
Table I. SPECTRUM OF AETIOLOGIES, ETHNIC DISTRIBUTION AND MORTALITY

                                      Gender        Ethnic group

Aetiology              No. (%)    Female   Male   African   Indian

Alcohol              198 (61.5)      15    183        81       80
Gallstones            44 (13.7)      35      9        24       16
Alcohol/gallstones     14 (4.3)       8      6         7        5
Idiopathic             21 (6.5)       9     12        10        7
Dyslipidaemia          26 (8.1)      22      4         3       21
Retroviral disease     16 (5.0)      13      3        16        0
Other                         3       3      0         2        1
  Total                     322     105    217       143      130

                        Ethnic group

Aetiology            Mixed race   White   Deaths (%)

Alcohol                     23      14     15 (7.6)
Gallstones                   2       2      4 (9.1)
Alcohol/gallstones           1       1     4 (28.5)
Idiopathic                   3       1      1 (4.7)
Dyslipidaemia                2       0     3 (11.5)
Retroviral disease           0       0      1 (6.3)
Other                        0       0            0
  Total                     31      18     28 (8.7)

TABLE II. COMPARISON OF SEVERITY SCORES AS PREDICTORS
OF OUTCOME IN REPRESENTATIVE SERIES

Author                  Year     No    Sensitivity

Glasgow Score
  Larvin (24)           1989    290         61
  Wilson et al. (25)    1990    160         77
  Tran and cuesta (26)  1992    259         58
  Taylor et al. (27)    2005     49         64
  This series           2007    322         57

Organ failure
  This series           2007    322         57

Author                  Specificity   PPV   NPV

Glasgow Score
  Larvin (24)                89       59    90
  Wilson et al. (25)         88       66    91
  Tran and cuesta (26)       89       68    84
  Taylor et al. (27)         73       67    70
  This series                92       37    94

Organ failure
  This series                88       37    96

PPV = positive predictive value; NPV = negative predictive value.

TABLE III. COMPARISON OF THE FREQUENCY OF AETIOLOGIES,
COMPLICATIONS AND DEATHS IN REPRESENTATIVE SERIES

Author                  Origin       Number       Alcohol

Ashley et al. (28)      USA          1 110        NS
Mann et al. (22)        England      631          30%
Toh et al. (23)         England      186          20%
Mofidi et al. (29)      Scotland     759          33%
Thomson et al. (12)     Scotland     378          15%
Carnovale et al. (30)   Italy        1 135        6.5%
Ricci et al. (31)       Italy        125          12%
John et al. (3)         S Africa     136          83%
Funnell et al. (2)      S Africa     99           74%
This series             S Africa     322          62%

                                                  Local
Author                  Gallstones   Idiopathic   complications

Ashley et al. (28)      NS           NS           NS
Mann et al. (22)        29%          NS           NS
Toh et al. (23)         33%          32%          15%
Mofidi et al. (29)      47%          13%          14%
Thomson et al. (12)     41%          20%          9%
Carnovale et al. (30)   68.7%        12.3%        NS
Ricci et al. (31)       76%          0%           NS
John et al. (3)         7%           7%           10%
Funnell et al. (2)      14%          7%           NS
This series             14%          7%           16%

                                     Mortality

                                                  Late
                                     Early        >2
Author                  Total        <2 wks       wks

Ashley et al. (28)      2%           29%          71%
Mann et al. (22)        9%           44%          56%
Toh et al. (23)         9%           NS           NS
Mofidi et al. (29)      6%           31%          69%
Thomson et al. (12)     8%           NS           NS
Carnovale et al. (30)   5%           51%          49%
Ricci et al. (31)       4%           NS           NS
John et al. (3)         8%           NS           NS
Funnell et al. (2)      13%          NS           NS
This series             9%           79%          21%
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