Abstract
Background
The inflammatory bowel diseases [IBD], including Crohn’s disease [CD] and ulcerative colitis [UC], frequently lead to bowel surgery. Hypoalbuminaemia has been shown to be a prognostic factor for outcomes following surgery for other indications, and we sought to determine its role in predicting IBD-related postoperative outcomes.
Methods
We included patients who underwent IBD-related major abdominal surgery in the American College of Surgeons’ National Surgical Quality Improvement Program [ACS-NSQIP] between 2005 and 2012. We assessed the impact of indicators of protein-energy malnutrition [PEM] including hypoalbuminaemia, weight loss, and body mass index on postoperative outcomes.
Results
We identified 10 913 IBD patients [6082 Crohn’s disease and 4831 ulcerative colitis] who underwent bowel surgery. The prevalence of modest and severe hypoalbuminaemia was 17% and 24%, respectively; 30-day mortality was higher in Crohn’s patients with modest and severe hypoalbuminaemia compared with those with normal albumin levels preoperatively [0.7% vs 0.2%, p <0.05; 2.4% vs 0.2%, p <0.01]. The same was true for patients with UC with modest and severe hypoalbuminaemia [0.9% vs 0.1%, p <0.01; 5.6% vs 0.1%, p <0.01]. Overall infectious complications were more common in the presence of severe hypoalbuminaemia for CD [20% vs 13%, p <0.01]. and UC [28% vs 15%, p <0.01] patients. Last, there were higher rates of extra-intestinal, non-septic complications in both CD and UC patients with hypoalbuminaemia compared with those with normal albumin levels.
Conclusions
This study suggests that moderate-severe hypoalbuminaemia is associated with worse IBD-related postoperative outcomes and may have a role in preoperative risk stratification.
Keywords: Crohn’s disease, malnutrition, hypoalbuminaemia, inflammatory bowel disease, postoperative complications, surgery, ulcerative colitis
1. Introduction
The inflammatory bowel diseases [IBD], which include Crohn’s disease [CD] and ulcerative colitis [UC], frequently lead to disease complications that require bowel surgery. Within 20 years of disease onset, 40% of CD patients and 15% of UC patients will require intestinal resection.1,2 Whereas surgery is curative for UC, nearly a third of CD patients who undergo surgery will require a second operation within 10 years.3
Serum albumin is an integral component of the preoperative assessment and has been shown to be a predictor of postoperative outcomes in non-cardiac surgeries.4 Hypoalbuminaemia may be particularly important in IBD because it is present in a fifth of patients even early in the course of disease, and may be a marker of the inflammatory process.5 Furthermore, hypoalbuminaemia is found in 25–80% of hospitalised UC patients and 25–50% of hospitalised CD patients.6 During inflammation, synthesis of albumin by the liver may be decreased by pathophysiological factors other than protein-calorie malnutrition. There may be increases in vascular permeability, and hepatic protein synthesis may be diverted toward other inflammatory cytokines.7
IBD patients whose disease is severe enough to require surgery likely have high inflammatory burden, and preoperative serum albumin may serve as a prognostic factor for postoperative morbidity and mortality. The American College of Surgeon’s National Surgical Quality Improvement Program [ACS-NSQIP] is a large, geographically representative, database of surgeries throughout the USA and Canada, which provides an important opportunity to characterise the relationship between preoperative hypoalbuminaemia and postoperative outcomes.
2. Methods
2.1. Study population
The ACS-NSQIP was created to measure short-term surgical outcomes and evaluate their predictors. Clinical information was prospectively collected from patients at 350 participating hospitals in the USA and Canada, who were at least 15 years old. The NSQIP has been previously described.8–12 We used ICD-9 codes to identify individuals undergoing IBD-related surgery between 2005 and 2012 with a diagnosis of Crohn’s disease [555.x] and ulcerative colitis [556.x].
2.2. Predictor variables
The primary predictor variable was hypoalbuminaemia, which was categorised as normal [≥3.5 g/dL], modest [3.0–3.4 g/dL], and severe [<3.0 g/dL]. We also measured body mass index [BMI], which was categorised as severely underweight [<16.00 kg/m2] underweight [16.00–18.50 kg/m2], normal [18.50–24.99 kg/m2], overweight [25.00–29.99 kg/m2], obese class I [30.00–34.99 kg/m2], obese class II [35.00–39.99 kg/m2], and obese class III [≥40.00 kg/m2]. Weight loss was defined as a greater than 10% decrease in body weight in the 6-month interval immediately preceding surgery. This dichotomous variable was derived by serial weights in the chart or patient report. Other demographic and clinical predictor variables included age, sex, smoking status, functional status, emergency status, and comorbidity as measured by the Charlson comorbidity index, which is a validated predictor of in-hospital outcomes including death.13,14 We also considered the type of surgery being performed as identified by CPT code: open or laparoscopic large or small bowel resection [CPT codes: 44005–44160; 44180–44238]; stoma formation [CPT codes: 44300–44346]; stricturoplasty [CPT codes: 44615]; fistula repair [CPT codes: 44602–44680]; and resection of the rectum [CPT codes: 45110–45397].
2.3. Outcome variables
Primary outcomes were: 30-day mortality; return to operating room; infectious complications [urinary tract infection, pneumonia, superficial and deep wound infections, intra-abdominal infection]; wound dehiscence; cardiac complications [myocardial infarction and cardiac arrest]; neurological complications [stroke and coma]; renal complications [acute renal failure and progressive renal insufficiency]; an inability to wean off ventilator; and venous thromboembolism [deep venous thrombosis, pulmonary embolism].
2.4. Statistical analysis
Analyses were performed using the Stata 14.0 SE software package [Stata Corp LP, College Station, TX]. Continuous variables were compared using the unpaired Student’s t test, and categorical variables were compared among categories of nutritional status using the chi square or Fisher’s exact test. Multiple logistic regression models were used to assess the association between nutritional indicators and postoperative outcomes while simultaneously adjusting for other predictors. The robust variance estimator was used to account for clustering.
3. Results
There were 10 913 IBD patients [6082 CD and 4831 UC] who underwent bowel surgery between 2005 and 2012. The prevalence of modest and severe hypoalbuminaemia was 17% and 24%, respectively. The demographic and clinical characteristics of patients with hypoalbuminaemia among CD and UC subgroups are shown in Table 1. There was a higher prevalence of underweight and severely underweight individuals among those with modest or severe hypoalbuminaemia. Those with modest or severe hypoalbuminaemia were more likely to have had >10% weight loss over the past 6 months. Preoperatively, these individuals were also more likely to be anaemic, have poor functional status, have greater comorbidity, and undergo emergent bowel surgery.
Table 1.
Demographic and clinical characteristics of inflammatory bowel disease patients undergoing bowel surgery.
| Preoperative hypoalbuminaemia | ||||||
|---|---|---|---|---|---|---|
| Crohn’s disease [n = 6082] | Ulcerative colitis [n = 4831] | |||||
| Normal [≥3.5 g/dL] [n = 3502] |
Modest [3.0-3.4 g/dL] [n = 1240] |
Severe [<3.0 g/dL] [n = 1340] |
Normal [≥3.5 g/dL] [n = 2888] |
Modest [3.0-3.4 g/dL] [n = 638] |
Severe [<3.0 g/dL] [n = 1305] |
|
| Mean age [y] [SD] | 41.1 ± 14.6 | 41.4 ± 15.9 | 42.9 ± 16.4* | 43.6 ± 15.5 | 46.2 ± 17.6* | 48.1 ± 18.0* |
| Female [%] | 1895 [54] | 669 [54] | 728 [54] | 1273 [44] | 272 [43] | 608 [47] |
| BMI category | * | * | * | * | ||
| Normal | 1638 [47] | 625 [51] | 678 [52] | 1201 [42] | 291 [46] | 599 [47] |
| Overweight | 945 [27] | 251 [21] | 222 [17] | 826 [29] | 174 [28] | 316 [25] |
| Obese-I | 371 [11] | 106 [9] | 88 [7] | 463 [16] | 72 [11] | 133 [11] |
| Obese-II | 155 [4] | 56 [5] | 43 [3] | 159 [6] | 32 [5] | 47 [4] |
| Obese-III | 91 [3] | 27 [2] | 37 [3] | 85 [3] | 16 [3] | 26 [2] |
| Underweight | 214 [6] | 125 [10] | 194 [15] | 104 [4] | 34 [5] | 113 [9] |
| Severely underweight | 37 [1] | 30 [2] | 54 [4] | 20 [1] | 11 [2] | 33 [3] |
| Weight loss [>10%] | 240 [7] | 156 [13]* | 294 [22]* | 124 [4] | 92 [14]* | 348 [27]* |
| Current smoking [%] | 972 [28] | 351 [28] | 375 [28] | 210 [7] | 51 [8] | 135 [10]* |
| Functional status [%] | * | * | * | |||
| Independent | 3460 [99] | 1204 [97] | 1238 [92] | 2859 [99] | 606 [95] | 1101 [84] |
| Partially dependent | 35 [1] | 29 [2] | 81 [6] | 20 [0.7] | 22 [3] | 128 [10] |
| Dependent | ≤5 [0.1] | 6 [0.5] | 21 [2] | 8 [0.3] | 10 [2] | 76 [6] |
| Anaemia [%] | 1503 [43] | 864 [70]* | 1198 [90]* | 1266 [44] | 494 [78]* | 1183 [91]* |
| Charlson comorbidity, mean [SD] | 0.05 ± 0.33 | 0.09 ± 0.56* | 0.18 ± 0.77* | 0.07 ± 0.45 | 0.14 ± 0.77† | 0.33 ± 1.05* |
| Emergent surgery [%] | 851 [24] | 334 [27] | 405 [30]* | 590 [20] | 154 [24] | 413 [33]* |
| Diabetes [%] | 102 [3] | 38 [3] | 82 [6]* | 175 [6] | 57 [9]* | 134 [10]* |
| Predicted morbidity [%] | 15% | 19%* | 27%* | 18% | 25%* | 37%* |
| Predicted mortality [%] | 0.3% | 0.7%* | 2.5%* | 0.5% | 2.0%* | 7.2%* |
SD, standard deviation; y, years; BMI, body mass index.
*p <0.01 compared with normal serum albumin; †p <0.05 compared with normal serum albumin.
The overall rate of postoperative complications, not including death, was 22% and 28% for CD and UC, respectively. The overall 30-day mortality following bowel surgery was 10.1 per 1000 for all IBD patients, 6.2 per 1000 for CD patients, and 14.5 per 1000 for UC patients.
3.1. Postoperative mortality and infectious complications based on hypoalbuminaemia
Short-term outcomes following bowel surgery among CD and UC subgroups, based on the degree of preoperative hypoalbuminaemia, are shown in Table 2; 30-day mortality was higher in Crohn’s patients with modest and severe hypoalbuminaemia, compared with those with normal albumin levels preoperatively [0.7% vs 0.2%, p <0.05; 2.4% vs 0.2%, p <0.01]. The same was true for patients with UC with modest and severe hypoalbuminaemia [0.9% vs 0.1%, p <0.01; 5.6% vs 0.1%, p <0.01]. Overall infectious complications were more common in the presence of severe hypoalbuminaemia for CD [20% vs 13%, p <0.01]. and UC [28% vs 15%, p <0.01] patients. Both CD and UC patients with severe hypoalbuminaemia before surgery were at increased risk of intra-abdominal infection, sepsis, sepsis leading to shock, and pneumonia. UC patients with severe hypoalbuminaemia preoperatively were at additional risk for urinary tract infections in the postoperative setting. The incidence of wound dehiscence was also found to be higher in CD patients with severe hypoalbuminaemia compared with those with normal albumin levels preoperatively [2.5% vs 1.3%, p <0.01]; the same was true in the UC subgroup [3.7% vs 1.1%; p <0.01].
Table 2.
Short-term outcomes following bowel surgery for inflammatory bowel disease.
| Preoperative hypoalbuminaemia | ||||||
|---|---|---|---|---|---|---|
| Crohn’s disease [n = 6082] | Ulcerative colitis [n = 4831] | |||||
| Normal [≥3.5 g/dL] [n = 3502] |
Modest [3.0-3.4 g/dL] [n = 1240] |
Severe [<3.0 g/dL] [n = 1340] |
Normal [≥3.5 g/dL] [n = 2888] |
Modest [3.0-3.4 g/dL] [n = 638] |
Severe [<3.0 g/dL] [n = 1305] |
|
| 30-day mortality | 7 [0.2] | 8 [0.7]† | 32 [2.4]* | ≤5 [0.1] | 6 [0.9]* | 73 [5.6]* |
| Postoperative complication‡ | 602 [17] | 247 [20]† | 466 [35]* | 620 [21] | 175 [27]* | 578 [44]* |
| Infectious complications | 447 [13] | 170 [14] | 271 [20]* | 444 [15] | 97 [15] | 367 [28]* |
| Deep wound | 63 [1.8] | 28 [2.3] | 35 [2.6] | 57 [2.0] | 6 [0.9] | 31 [2.4] |
| Intra-abdominal | 220 [6.3] | 73 [5.9] | 114 [8.5]† | 200 [6.9] | 45 [7.1] | 139 [11]* |
| Sepsis | 181 [5.2] | 77 [6.2] | 118 [8.8]* | 175 [6.1] | 46 [7.2] | 164 [13]* |
| Septic shock | 42 [1.2] | 13 [1.1] | 45 [3.4]* | 28 [1.0] | ≤5 [0.8] | 63 [4.8]* |
| Pneumonia | 57 [1.6] | 17 [1.4] | 41 [3.1]* | 30 [1.0] | 13 [2.0]† | 77 [5.9]* |
| Urinary tract infection | 94 [2.7] | 33 [2.7] | 47 [3.5] | 122 [4.2] | 20 [3.1] | 81 [6.2]* |
| Wound dehiscence | 44 [1.3] | 11 [0.9] | 33 [2.5]* | 33 [1.1] | 11 [1.7] | 48 [3.7]* |
| Bleeding requiring transfusion | 124 [3.5] | 78 [6.3]* | 214 [16.0]* | 137 [4.7] | 74 [12]* | 239 [18]* |
| Cardiac complications | 11 [0.3] | ≤5 [0.3] | 12 [0.9]† | ≤5 [0.1] | ≤5 [0.8]* | 25 [1.9]* |
| Myocardial infarction | 7 [0.2] | ≤5 [0.1] | 7 [0.5] | ≤5 [0.1] | ≤5 [0.5]† | 11 [0.8]* |
| Cardiac arrest | 4 [0.1] | 3 [0.2] | 6 [0.5] | ≤5 [0] | ≤5 [0.3] | 15 [1.2]* |
| Neurological complications | ≤5 [0.1] | ≤5 [0.2] | ≤5 [0.4]† | ≤5 [0.1] | ≤5 [0.6]† | 14 [1.1]* |
| Cerebrovascular accident | ≤5 [0] | ≤5 [0.1] | ≤5 [0.2] | ≤5 [0] | ≤5 [0] | 8 [0.6]* |
| Coma | ≤5 [0] | ≤5 [0] | ≤5 [0.1] | ≤5 [0] | ≤5 [0.3]† | ≤5 [0.4]* |
| Peripheral nerve injury | ≤5 [0] | ≤5 [0.2] | ≤5 [0.2] | ≤5 [0] | ≤5 [0.3] | ≤5 [0.1] |
| Renal complications | 22 [0.6] | 11 [0.9] | 18 [1.3] | 31 [1.1] | 12 [1.9] | 37 [2.8]* |
| Acute renal failure | 8 [0.2] | ≤5[0.2] | 11 [0.8]† | 6 [0.2] | ≤5 [0.6] | 22 [1.7]* |
| Progressive renal insufficiency | 14 [0.4] | 8 [0.7] | 9 [0.7] | 25 [0.9] | 9 [1.4] | 16 [1.2] |
| Venous thromboembolism | 46 [1.3] | 18 [1.5] | 57 [4.3]* | 65 [2.3] | 27 [4.2]* | 84 [6.4]* |
| Deep venous thrombosis | 36 [1.0] | 14 [1.1] | 46 [3.4]* | 52 [1.8] | 19 [3.0] | 69 [5.3]* |
| Pulmonary embolism | 15 [0.4] | ≤5 [0.3] | 21 [1.6]* | 14 [0.5] | 13 [2.0]* | 22 [1.7]* |
| Failure to wean off ventilator | 26 [0.7] | 21 [1.7]* | 58 [4.3]* | 22 [0.8] | 13 [2.0]* | 126 [9.7]* |
| Return to operating room | 221 [6.3] | 70 [5.7] | 117 [8.7]* | 195 [6.8] | 55 [8.6] | 166 [13]* |
‡Any postoperative complication excluding death.
*p <0.01 compared with normal serum albumin; †p <0.05 compared with normal serum albumin.
3.2. Other postoperative complications based on hypoalbuminaemia
Postoperative bleeding requiring transfusion was more prevalent among CD patients with modest or severe hypoalbuminaemia compared with those with normal albumin levels preoperatively [6.3 vs 3.5%, p <0.01; 16.0 vs 3.5%, p <0.010]. The same trend was seen in UC patients with modest or severe hypoalbuminaemia [12 vs 4.7%, p <0.01; 18 vs 4.7%, p <0.01]. Additionally, cardiac complications postoperatively occurred more frequently in both CD and UC patients with severe preoperative hypoalbuminaemia compared with those patients with normal albumin levels [0.9% vs 0.3%, p <0.05; 1.9% vs 0.1%, p <0.01]. Similarly, neurological complications postoperatively occurred at a higher frequency in both subgroups of CD and UC patients with severe preoperative hypoalbuminaemia compared with CD and UC patients with normal albumin levels [0.4% vs 0.1%, p <0.05; 0.8% vs 0.1%, p <0.01]. Whereas UC patients with severe hypoalbuminaemia had a higher rate of renal complications compared with those UC patients with normal albumin levels [2.8% vs 1.1%, p <0.01], we did not find a statistically significant difference between similar CD subgroups [Table 2].
There was a higher rate of failure to wean off ventilators in patients with both modest and severe preoperative hypoalbuminaemia compared with those with normal preoperative albumin levels in both CD and UC subsets [1.7% and 4.3% vs 0.7%, p <0.01; 2.0% and 9.7% vs 0.8%, p <0.01]. Rates of venous thromboembolism were higher in both CD and UC patients with severe hypoalbuminaemia compared with those with normal levels [4.3% vs 1.3%, p <0.01; 6.4% vs 2.3%, p <0.01]. Last, the rate of return to the operating room for major surgery within 30 days was higher among those with severe hypoalbuminaemia preoperatively for both CD [8.7% vs 6.3%, p <0.01] and UC [13% vs 6.8%, p <0.01] subgroups [Table 2].
3.3. Multivariable regression analysis
In multiple logistic regression, severe hypoalbuminaemia [<3.0 g/dL] was associated with postoperative complications [not including death] in both CD (odds ratio [OR], 1.93; 95% confidence interval [CI]: 1.64–2.28) and UC [OR, 2.08; 95% CI: 1.75–2.48] after adjusting for BMI, weight loss, age, sex, comorbidity, emergent status, smoking status, functional status, presence of preoperative anaemia, and year of surgery [Table 3]. In CD, the risk of postoperative complications was increased if the patient was preoperatively underweight [OR, 1.26; 95% CI: 1.01–2.29] or severely underweight [OR, 1.52; 95% CI: 1.01–1.57]. Being underweight or severely underweight was not associated with postoperative outcomes in UC [Table 3]. Interestingly, all three subclasses of obesity were associated with worse postoperative outcomes in CD [Table 3], but only class 2 obesity was associated with postoperative complications in UC [OR, 1.43; 95% CI: 1.06–1.93].
Table 3.
Multivariable logistic regression analysis to assess predictors of postoperative complications following bowel surgery for Crohn’s disease and ulcerative colitis.
| Crohn’s disease Adjusted odds ratio [95% CI] |
Ulcerative colitis Adjusted odds ratio [95% CI] |
|||
|---|---|---|---|---|
| Preoperative albumin | ||||
| Normal [≥3.5 g/dL] | ref | ref | ||
| Modest hypoalbuminaemia [3.0–3.4 g/dL] | 1.05 [0.88–1.25] | 0.606 | 1.16 [0.84–1.42] | 0.170 |
| Severe hypoalbuminaemia [<3.0 g/dL] | 1.93 [1.64–2.28] | <0.001 | 2.08 [1.75–2.48] | <0.001 |
| Body mass index | ||||
| Normal | ref | ref | ||
| Overweight | 1.07 [0.91–1.27] | 0.408 | 0.96 [0.82–1.13] | 0.643 |
| Obese-I | 1.50 [1.21–1.86] | <0.001 | 1.03 [0.84–1.27] | 0.773 |
| Obese-II | 1.58 [1.16–2.15] | 0.004 | 1.43 [1.06–1.93] | 0.018 |
| Obese-III | 1.58 [1.09–2.29] | 0.016 | 1.10 [0.74–1.63] | 0.647 |
| Underweight | 1.26 [1.01–2.29] | 0.042 | 0.89 [0.66–1.22] | 0.480 |
| Severely underweight | 1.52 [1.01–1.57] | 0.047 | 1.07 [0.61–1.89] | 0.808 |
| Weight loss | 1.13 [0.93–1.37] | 0.23 | 0.98 [0.79–1.21] | 0.826 |
| Age | 1.01 [1.00–1.01] | <0.001 | 1.01 [1.01–1.02] | <0.001 |
| Female sex | 1.16 [1.02–1.32] | 0.029 | 0.95 [0.83–1.09] | 0.473 |
| Charlson Index | 1.19 [1.05–1.34] | 0.005 | 1.22 [1.11–1.35] | <0.001 |
| Emergent surgery | 1.13 [0.97–1.31] | 0.130 | 1.20 [1.02–1.40] | 0.026 |
| Active smoking | 1.19 [1.03–1.37] | 0.020 | 1.22 [0.96–1.55] | 0.108 |
| Functional status [%] | ||||
| Independent | ref | ref | ||
| Partially dependent | 1.97 [1.37–2.82] | <0.001 | 1.46 [1.03–2.06] | 0.032 |
| Dependent | 4.37 [1.76–10.9] | 0.002 | 2.21 [1.32–3.68] | 0.002 |
| Anaemia | 1.48 [1.27–1.73] | <0.001 | 1.31 [1.12–1.54] | 0.001 |
| Year of operation | 1.09 [1.05–1.14] | <0.001 | 1.09 [1.05–1.14] | <0.001 |
CI, confidence interval; ref, reference.
4. Discussion
Our study has shown that preoperative hypoalbuminaemia in both CD and UC was associated with higher 30-day postoperative mortality and complications. The association of severe hypoalbuminaemia with poor postoperative outcomes was independent of low body mass index and preoperative weight loss. Our study provides a nationally representative large sample size that enabled us to compare very specific outcomes between those with and without hypoalbuminaemia.
In our study, low serum albumin is likely a marker of systemic inflammation. Serum albumin is a negative acute phase reactant and decreases in proinflammatory states due to increased vascular permeability, increased clearance, and alterations in liver synthesis.7 Low albumin is not uncommonly misattributed to malnutrition. However, protein-calorie malnutrition does not usually lead to significant hypoalbuminaemia in the absence of inflammation. For example, patients with anorexia nervosa usually have normal or only slightly decreased serum albumin despite very low nutritional intake.15 In our study, low body mass index and hypoalbuminaemia were both independent predictors of postoperative complications. In our IBD population, the cause of low serum albumin may also be multifactorial, arising from systemic inflammation, malnutrition, or both. Therefore, formal assessment of nutritional status through tools such as the Subjective Global Assessment [SGA] may be helpful in identifying those who may benefit from nutritional support.16
Our findings are supported by other recent studies examining short-term predictors of outcome, but other smaller-scale studies have found conflicting results in CD.17–21 Certainly, our findings are in keeping with those of the National Veterans Affairs Surgical Risk Study, which identified serum albumin as the most important predictor of 30-day morbidity and mortality in 54 215 major non-cardiac operations.4
The second important finding of our study is that overall infectious complications were more common in the presence of severe hypoalbuminaemia for both CD [20% vs 13%; p <0.01] and UC [28% vs 15%; p <0.01] patients. Smaller studies have found a similar inverse relationship between preoperative albumin levels and rates of septic complications.22–27 On the other hand, Tay et al. found that intra-abdominal septic complications were not influenced by albumin levels.27 Notably, however, their study was limited to only 100 CD patients undergoing segmental resection with primary anastomosis or stricturoplasty, and their cut-off for hypoalbuminaemia was defined as values below 3.0 g/dL, which differs from our cutoff of less than 3.5 g/dL.
Third, our study found that preoperative hypoalbuminaemia was associated with an increased risk of need for blood transfusion as well as non-septic complications, including cardiac, neurological, respiratory, renal, and thromboembolic complications. Similarly, Hiemann et al. found that patients with a low preoperative serum albumin concentration had a significantly higher incidence of non-septic complications.28 These findings further suggest that hypoalbuminaemia may be a surrogate indicator of severe IBD and prognostic indicator of systemic complications.
Last, the rate of return to the operating room for major surgery within 30 days was higher amongst those with severe hypoalbuminaemia for both CD [8.7% vs 6.3%, p <0.01] and UC [13% vs 6.8%, p <0.01]. In a study of postoperative outcomes after laparoscopic total abdominal colectomy with end ileostomy for UC, preoperative hypoalbuminaemia was also found to be associated with reoperation.29
Among the other important predictors of postoperative outcomes in our study were preoperative functional status and body mass index [BMI], both of which were independent of hypoalbuminaemia. Though individuals who were not functionally independent accounted for less than 10% of patients undergoing IBD surgery, they had 2- to 4-fold higher risk of postoperative complications. Functional status likely reflects disease activity so severe that it is debilitating. Interestingly, for CD, being severely obese and underweight were both associated with worse postoperative outcomes. Being underweight may be a sign of protein-calorie malnutrition which may affect wound healing.30 Because the association of being underweight with postoperative outcomes was independent of hypoalbuminaemia, this would suggest that the latter is not an indicator of malnutrition. Obesity has been previously described to be associated with worse postoperative complications, particularly wound dehiscence, in the general population across a gamut of gastrointestinal surgeries.31 These observations are particularly relevant since the prevalence of obesity among CD patients undergoing surgery seems to be rising in North America, and BMI should be taken into account in preoperative planning.32
Our study had several limitations. First, though the NSQIP is a prospective multicentre study, it did not capture important clinical parameters such as disease severity and phenotype that predict IBD-related outcomes. Since albumin is a negative acute phase reactant, severe hypoalbuminaemia may be a marker of severe IBD which may predispose to worse postoperative outcomes. As an example, those with more severe disease may be more likely to be on immunosuppressants that can contribute to infectious complications. Our study did not document or adjust for types of IBD medications. However patients in our study population, all of whom have undergone IBD-related surgery, already represent a subgroup of patients with at least moderate-severe disease course. Our analysis did account for whether IBD surgery was performed emergently, which is a crude indicator of the severity of disease presentation.
Despite the above limitations, this study has definitively established the association between preoperative hypoalbuminaemia and short-term postoperative outcomes in the largest IBD surgical cohort to date. It reinforces findings from other observational studies in populations that were not specific to IBD. The large sample size has enabled us to identify less common extra-intestinal sequelae, including thromboembolic, respiratory, and cardiac complications. In patients with hypoalbuminaemia, increased vigilance should be exercised to detect early and mitigate life-threatening complications such as sepsis and venous thromboembolism [VTE]. Optimising process measures for managing indwelling catheters, and implementation of infection control procedures and VTE prophylaxis, may reduce some of the impact of preoperative hypoalbuminaemia on postoperative complications. Importantly, as a prognostic indicator, preoperative albumin levels may enable surgeons to stratify risk of postoperative complications and inform their patients accordingly.
Funding
GCN is supported by a New Investigator Award and an Embedded Clinician Researcher Award by the Canadian Institutes of Health Research. The sponsor had no role in any aspect of the study.
Conflict of Interest
The authors report no conflict of interest.
Acknowledgments
The American College of Surgeons National Surgical Quality Improvement Program and the hospitals participating in the ACS NSQIP are the sources of the data used herein; they have not verified and are not responsible for the statistical validity of the data analysis or the conclusions derived by the authors.
Author Contributions
GCN, LD, and TDJ conceived of and designed the study. GCN and RYC conducted all analyses. The manuscript was drafted by GCN and critically reviewed and edited by all authors.
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