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IAH and ACS: Effects on patient outcome

Ideally we would practice medicine based on multicenter randomized controlled trials demonstrating improvements in outcome. Unfortunately – well over 90% of medical practice –is not based on RCT’s and perhaps not even based on high levels of evidence. In terms of interventions to change outcomes in IAH/ACS we also await level 1 evidence in terms of several multicenter randomized controlled trial outcome studies – and it appears highly unlikely such studies will be conducted in the near future given the increasing non-level 1 evidence that does demonstrate improved outcomes if protocols are implemented to reduce IAP prior to the onset of abdominal compartment syndrome. There is, in fact, a very large volume of outcome data that is fairly compelling.

First, the data is very clear from large studies that there is a correlation between elevated intra-abdominal pressure and worse outcome in terms of organ failure, ICU length of stay and mortality. Malbrain et al in 2005 demonstrated this conclusively in a multicenter trial showing even "mild" elevations of IAP (>12 mmHg) lead to worse outcomes probably due to the prolonged organ ischemia that occurs.[1] Sugrue et al in 1999 showed elevated IAP (over 18 mm Hg) was an independent predictor of renal failure, ranking up with hypotension, age and sepsis.[2] Vidal found 64% of patients in a mixed ICU population had IAH, which was an independent risk factor for organ dysfunction and death.[3] Pupelis prospectively collected IAP and outcome data on pancreatitis patients and also found significant differences in outcomes.  Those patients with IAP less than 18 mm Hg had no mortality, 19% incidence of MODS/SIRS and mean ICU length of stay of 9 days whereas patients with IAP greater than 18 mm Hg had 36% mortality, 64% incidence of MODS/SIRS and mean ICU length of stay of 21 days.[4] In a follow-up study investigating the results of interventions on outcome – these same authors demonstrated a reduced mortality and less resource consumption when they implemented an early medical protocol (rather than late surgery) in patients with pancreatitis.[5] These authors conclude - “Routine measurement of the intra-abdominal pressure is rational in the clinical setting of the ICU and gives additional criteria for the evaluation of the clinical course and the effectiveness of the treatment.” Biancofiore prospectively followed 108 liver transplant patients and noted that those who developed elevated intra-abdominal pressures had substantially higher incidences of death, renal failure and the need for permanent dialysis.[6]  They conclude – “The critical IAP values… with the best sensitivity specificity, were 23 mm Hg for postoperative ventilatory delayed weaning (P <.05), 24 mm Hg for renal dysfunction (P <.05), and 25 mm Hg for death (P <.01).”Many, many studies show similar correlations in patients with liver failure, trauma, pancreatitis, sepsis, ruptured aneurysms, etc.[7-14]

It is clear form this data that elevated IAP is a marker for worse outcome. The important question then is can we impact these outcomes through prevention or treatment (monitor, detect and intervene)?  The answer is yes and more and more studies to support this conclusion.  There are multiple case series and case reports showing situations where dying patients had their outcomes reversed by interventions that reduced IAP once the abdominal compartment syndrome was recognized.  However, there are also numerous interventional studies on larger groups demonstrating you can improve outcomes in a group overall if you measure IAP and intervene aggressively:

Ten years ago Ivatury showed that prophylactic interventions to reduce IAH/ACS in major trauma cases led to dramatic outcome improvement (ACS reduction from 52% to 22%, death reduction from 36% to 11% - relative mortality reduction of 69%).[15] Joseph et al noted that IAP monitoring and treatment with laparotomy was instrumental in improving outcome in their neurotrauma/stroke patients with elevated ICP - they now advocate aggressive IAP monitoring and interventions in all patients with ICP bolts.[16] Oda demonstrated that aggressive IAP monitoring with early CRRT once IAP increased to more than 15 mm Hg (using a filter specifically designed for removal of cytokines) in cases of severe pancreatitis resulted in a huge reduction in their traditional mortality (>30% down to 6%).[17] Sun et al, in a prospective randomized trial, were able to cut hospital length of stay in half and reduce pancreatitis mortality from 20% to 10% using IAP monitoring to guide interventional strategies.[18] Cheatham noted marked reductions in the need for open abdominal management (13% absolute, 46% relative reduction), length of stay in the hospital (reduced by 10 days), mortality (49% down to 28% or 42% relative mortality reduction) and cost of care following the introduction of a protocol for early medical management of IAH/ACS.[19] Ennis introduced a fluid and IAP management protocol into the military burn setting of the Iraq war, resulting in a dramatic reduction in the incidence of ACS as well as an improvement in overall survival (32% mortality prior, 18% mortality after – relative mortality reduction of 43%).[20] Mullens’ found that goal directed reduction of IAP via simple fluid removal (CVVH or paracentesis) for the treatment of decompensated CHF was much more successful in treating CHF induced renal dysfunction than any hemodynamic optimization strategies.[12, 13] Batacchi began measuring IAP on critical surgical patients in the operating room at the time of closure.[21] If the IAP was over 12 mm Hg they left the abdomen open and randomized to passive drainage versus negative pressure drainage.  Open cases with negative pressure drainage had quicker drops in the IAP, 4 fewer days on the ventilator, fewer days in the ICU and less mortality and morbidity than passively treated patients. Kimball prospectively followed 600 patients (over 5 years) undergoing IAP monitoring (not all of them developed IAH) and investigated the impact of a management protocol introduced following the first year of data collection.[22] These investigators found a reduction in mortality of 3.3% (relative mortality reduction of 18%) even in this low risk group. Furthermore they reduced open abdominal management from 23% to 13% (40% relative reduction) and reduced ICU length of stay and days on the ventilator by over 4 days.  Their calculated reduction in charges during the final year of management was over 3 million dollars compared to the initial year.

Despite all this information, it needs to be very clear that treatment for IAH and ACS does not guarantee a good outcome. As demonstrated by both Oda and Sun, it is much better to detect this syndrome in the early stages (IAH) and intervene in an urgent medical fashion prior to the onset of overt organ failure (ACS). For this reason the World Society of Abdominal Compartment Syndrome strongly recommends early medical intervention and provides algorithms for implementing this management at their web site (CLICK HERE FOR DOWNLOADABLE ALGORITHMS) as well as a well written summary of how to apply their suggestions at the bedside (CLICK HERE FOR AN ARTICLE BY DR. CHEATHAM DISCUSSING MEDICAL MANAGEMENT SUGGESTIONS) Patients who end up with ACS are extremely ill, often requiring emergent therapies including very invasive surgery and many die no matter what the clinician does to intervene.  However, there is clear evidence that intervention for both IAH and for ACS definitely improves outcomes in some patients who would otherwise die.

Below is a brief summary of many of these articles:

Randomized Controlled trials:

Sun, World J Gastro 2006 - Pancreatitis patients[18]

These authors randomized their fulminate acute pancreatitis patients into two groups.  Both groups received routing non-operative care including hemofiltration.  The study group also had their IAP monitored and had a continuous indwelling paracentesis catheter placed to drain off excess cytokine rich peritoneal fluid (even if none was visible). Groups were compared for changes in APACHE II scores, length of hospitalization and survival to hospital discharge.  The interventional group did much better in all parameters – APACHE II scores dropped significantly by day 2, hospital length of stay was half (15 days vs. 28 days) and mortality was half (10% vs. 20%).

Mullens, J Cardiac Failure 2009 – CHF patient population[12]

Small trial on 9 patients suffering acutely decompensated heart failure. The authors found that hemodynamic optimization have little effect on renal function and diuresis. However, after noting all these patients had an elevated IAP, they implemented medical treatment strategies for IAP (CVVH or paracentesis) and successfully reduced IAP in all patients, resulting in improved renal perfusion and marked improvement in renal function.

Kaplan, The American Surgeon 2011 - Trauma population of open abdomens [31]

A recent RCT was completed showing the type of temporary abdominal closure technique chosen makes a huge difference in outcome and cost of care. Despite the cheaper option of a Bogota bag, it does not mobilize cytokine rich fluids as well,  has a markedly increased rate of fistula formation (50%) a longer delay to closure (29 days),  fewer successful closures (70%) and higher mortality (27%) than commercially available negative pressure dressings (0-4%; 4.3 -6.4 days, 94%, 16% respectively). (Abstract only, paper in process as of Sept 2011)

Du, Pancreas 2011 - Severe Acute Pancreatitis population [32]

This study investigated the value of resuscitation of 41 severe acute pancreatitis patients with either hydroxyethyl starch (HES) or ringer's lactate (LR) solution. Their primary endpoint was IAP. The secondary end points were fluid balance, major organ complications, the Acute Physiology and Chronic Heath Evaluation II score, and the serum levels of C-reactive protein, interleukin-6, and interleukin-8. In the HES group, the IAP was significantly lower in 2 to 7 days, and fewer patients received mechanical ventilation (15.0% vs 47.6%). A negative fluid balance was observed earlier in the HES group than in the RL group (2.5 +/- 2.2 vs 4.0 +/- 2.5 days). They conclude that fluid resuscitation with HES in the early stages of SAP can decrease the risk of intra-abdominal hypertension and reduce the use of mechanical ventilation.

Interventional before and after studies or non-randomized trials:

Kimball, Acta Clin Belgica 2009 – SICU population[22]

Kimball, Am Surg 2011 - SICU population[29]

600 patients at risk for IAH/ACS over 5 years were prospectively followed and monitored. These investigators found a reduction in mortality of 3.3% (relative mortality reduction of 18%) even in this low risk group. Furthermore they reduced open abdominal management from 23% to 13% (40% relative reduction) and reduced ICU length of stay and days on the ventilator by over 4 days with a corresponding decrease in VAP rates presumed to be due to earlier extubation (there was no change in the low VAP rate in their non-IAH cohort).  Their calculated reduction in charges during the final year of management was over 3 million dollars with about a 20 thousand dollar cost in supplies and nursing time compared to the initial year. 

Cheatham, Acta Clin Belgica 2010 – SICU population[19]

388 patients over 5 years prospectively followed. Medical management protocol introduced during the last two years. Resulted in marked reductions in the need for open abdominal management (13% absolute, 46% relative reduction), length of stay in the hospital (reduced by 10 days), mortality (49% down to 28% or 42% relative mortality reduction) and cost of care.

Podcast of Dr. Cheatham discussing this research 4-20-2010:

http://itunes.apple.com/us/podcast/sccm-podcast-icritical-care/id76207297

Cheatham, Am Surgeon 2011 - SICU population[30]

This article reviews the Orlando Florida groups experience in terms of costs of care for their highest risk population - those treated with an open abdomen. When they started care the only intervention they had was decompressive surgery for severely advanced ACS. These patients tended to be had abdominal closures in an average of 39 days. The average hospital charge for this group was $598 thousand dollars. As time progressed and these clinicians recognized the value of earlier opening for ACS, implementation of the WSACS medical treatment protocol, continued IAP monitoring and active management of the bowel to reduce IAP and close the abdomen sooner (average closure 5 days) they found reductions in charges to these very expensive patients with average costs of $227 thousand dollars per patient. These cost reductions were also complemented by much better survival rates (see table and graphs below).

Resource utilization for patients with open abdomens

Outcome of patients being treated for IAH with multimodal medical and surgical interventional protocol

Cheatham, ,Chest 2011 - Mixed ICU population [33]

These authors investigated the effect of percutaneous drainage of free intra-peritoneal fluid on intervention requirements for patients who were advancing to ACS and were being considered for decompressive surgery. Prior to surgical therapy, the the patient had free fluid on ultrasound that could be drained, surgical intervention was avoided in as many as 80% of cases. (Cheatham, Chest 2011 - in process) Given the high costs and morbidity associated with decompressive surgery, this intervention can result in a huge reduction in resource consumption. Following these impressive results these authors have instituted mandatory ultrasound to assess for free fluid in every case of IAH where the IAP exceeds 15 mm Hg. If free fluid is sited the ultrasound is used to guide percutaneous drainage and the catheter is left in place for a few days to continue removing the inflammatory liquid.

Batacchi, Critical Care 2009 – SICU population.[21]

66 patients with emergent abdominal surgery prospectively managed and compared to historical controls. The IAP was measured in the operating room at the time of facial closure – if over 12 mm Hg the sutures were released, the abdomen was dressed open with a VAC device and active removal of fluid from the abdominal cavity was achieved. Compared to passive historical therapy this resulted in high rates of primary closure, fewer days on the ventilator and ICU and less resource consumption.

Pupelis, HBP 2008 – Pancreatitis population[5]

274 patients with severe acute pancreatitis admitted to an ICU were reviewed for outcomes following the introduction of a protocol that reiterated early medical management of IA before the onset of ACS.  In the pre-protocol era mortality was 19% and open abdominal management was 40%.  Following protocol implementation fewer cases of ACS developed, mortality dropped to 12% (absolute reduction of 7%, relative reduction of 36%) and open abdominal management dropped to 19% (absolute reduction of 21%, relative reduction of 52%)

Ennis, J Trauma 2008 – Burn population[20]

118 patients with burns over 30% were studied before (56) and after (62) implementation of a protocol designed to reduce ACS and organ failure.  Following protocol implementation a dramatic reduction in the incidence of ACS as well as an improvement in overall survival resulted (32% mortality prior, 18% mortality after – relative mortality reduction of 43%).

 Ivatury, J Trauma 1998- Trauma surgery[15]

70 damage control laparotomy patients comparing open vs. closed abdomen treatment. First 25 had facial closure – 52% developed abdominal compartment syndrome and 39% died.  Last 45 cases were treated with open abdomen, 22% developed abdominal compartment syndrome and 10.9% died.

 Oda, Ther Apher 2005 - Pancreatitis[17]

Traditional mortality for severe acute pancreatitis in this ICU was over 25%.  These authors sought to reduce this mortality by early aggressive continuous hemofiltration in patients who developed IAP of 15 mmHg or higher.  They prospectively entered 17 patients and were able to dialyze off interleukin 6 (an inflammatory cytokine) as well as excess extravascular water, resulting in a drop in intra-abdominal pressure in all patients to less than 10 mm Hg and a 94% survival rate.

 Rasmussen, J Vasc Surg 2002 – Aortic Aneurysm surgery[23]

Study comparing treatment of ruptured aortic aneurysm with open abdomen vs. closure and re-opening if IAH developed. 35 patients were initially treated with open abdomen after ruptured AAA repair – mortality 51%, multiple organ failure 11%. 10 patients were closed primarily and developed ACS requiring decompressive surgery – mortality 70%, multiple organ failure 70%.

Tao, J Huazhong Univ Sci Technolog Med Sci 2003 - Pancreatitis[24]

23 cases of severe acute pancreatitis who developed abdominal compartment syndrome. 18 were treated with aggressive intervention and early decompressive surgery – 16.7% mortality. 5 were observed, no ACS intervention – 80% mortality.

 Observational outcome studies

 Malbrain, Crit Care Med, 2005 – Mixed ICU population outcome[1]

Prospective, multi-center trial looking at incidence and outcome of patients with sub-acute intra-abdominal hypertension of only 12 mm Hg or more (a level that reduces essential organ perfusion but does not cause the abdominal compartment syndrome). 265 patients were entered. In patients with an IAP < 12 mm Hg the mortality was 22.2%, (lower APACHE quartiles mortality <3%). In cases with IAP > 12 mm Hg the mortality was 38.8% (lower APACHE quartiles mortality 15-30%).

 Pupelis: Acta Chir Belg 2002 - Pancreatitis[4]

37 cases of severe acute pancreatitis observed for outcome. 26 cases maintained IAP less than 18 mm Hg – no mortality, 19% MODS, 9 day ICU LOS. 11 cases with IAP over 18 mm Hg – 36% mortality, 64% MODS, 21 day ICU LOS

 Biancofiore, Transplant Proc 2004 – Liver transplant[6]

108 liver transplant cases observed for outcome. 32% developed IAP > 18 mm Hg, 1/3 developed acute renal failure, 9% required permanent dialysis, mortality higher.  68% never developed IAH, 8% had acute renal failure, none required permanent dialysis

 Raeburn, Am J Surg 2001 – Trauma surgery[25]

77 patients with damage control surgery. 36% developed IAP over 20 mm Hg – these patients had longer LOS, longer ventilator times, higher incidence of MOF, higher mortality

 Joseph, J Trauma 2004 – Neurotrauma with elevated ICP[16]

17 patients with intractable ICP (mean 30 mm Hg) despite maximal intervention including removal of upper skull in 14.  Mean IAP was 27 mm Hg.  All had decompressive laparotomy to treat their ICP.  100% had ICP reduction to a mean of 17 mm HG.  11 of 17 had persistently lower ICP and all lived with “good neurologic outcomes.”  Authors now “routinely measure intra-abdominal pressure every 2-4 hours” and conclude that decompression should occur before obvious symptoms of abdominal compartment syndrome.

 Ejike, Critical Care Medicine 2005 – General Pediatric ICU[26]

17.6% of mechanically ventilated pediatric patients had abdominal compartment syndrome (defined as IAP> 12 mm Hg plus 2 organ failures). In this group the median IAP was 18 mm Hg, the mean ICU length of stay was 13 days and the mortality was 33.3%.  The remaining children did not have ACS, their mean length of stay was 6 days and their mortality was 2.4%. 

 Cipolla, Am Surg 2005[27]

20 patients with complicated abdominal surgery managed with an open abdomen and an algorithm for treatment based on intra-abdominal pressures.  Predicted mortality was 73% based on simplified acute physiology scores. Actual mortality was 5.9%.

 Reintam, Intensive Care Medicine 2005 – General ICU outcome[28]

113 patients were monitored for IAP over 12 mm Hg.  In those with IAP> 12 mm Hg the mortality was 50%, whereas those with normal IAP had mortality of 18%. Odds ratio of death with IAP over 12 mm Hg was 9.2 in medical ICU patients, and 1.4 in surgical patients.

References:

1.          Malbrain, M.L.N.G., et al., Incidence and prognosis of intraabdominal hypertension in a mixed population of critically ill patients: a multiple-center epidemiological study. Crit Care Med, 2005. 33(2): p. 315-22.

2.          Sugrue, M., et al., Intra-abdominal hypertension is an independent cause of postoperative renal impairment. Arch Surg, 1999. 134(10): p. 1082-5.

3.       Vidal, M.G., et al., Incidence and clinical effects of intra-abdominal hypertension in critically ill patients. Crit Care Med, 2008. 36(6): p. 1823-31.

4.          Pupelis, G., et al., Clinical significance of increased intraabdominal pressure in severe acute pancreatitis. Acta Chir Belg, 2002. 102(2): p. 71-4.

5.          Pupelis, G., et al., Conservative approach in the management of severe acute pancreatitis: eight-year experience in a single institution. HPB (Oxford), 2008. 10(5): p. 347-55.

6.          Biancofiore, G., et al., Intraabdominal pressure in liver transplant recipients: incidence and clinical significance. Transplant Proc, 2004. 36(3): p. 547-9.

7.       Al-Bahrani, A.Z., et al., Clinical relevance of intra-abdominal hypertension in patients with severe acute pancreatitis. Pancreas, 2008. 36(1): p. 39-43.

8.          Daugherty, E.L., et al., Abdominal compartment syndrome is common in medical intensive care unit patients receiving large-volume resuscitation. J Intensive Care Med, 2007. 22(5): p. 294-9.

9.       Tao, H.Q., J.X. Zhang, and S.C. Zou, Clinical characteristics and management of patients with early acute severe pancreatitis: experience from a medical center in China. World J Gastroenterol, 2004. 10(6): p. 919-21.

10.          Leppaniemi, A., K. Johansson, and J.J. De Waele, Abdominal compartment syndrome and acute pancreatitis. Acta Clin Belg Suppl, 2007(1): p. 131-5.

11.          Regueira, T., et al., Intra-abdominal hypertension: incidence and association with organ dysfunction during early septic shock. J Crit Care, 2008. 23(4): p. 461-7.

12.          Mullens, W., et al., Prompt reduction in intra-abdominal pressure following large-volume mechanical fluid removal improves renal insufficiency in refractory decompensated heart failure. J Card Fail, 2008. 14(6): p. 508-14.

13.          Mullens, W., et al., Elevated intra-abdominal pressure in acute decompensated heart failure: a potential contributor to worsening renal function? J Am Coll Cardiol, 2008. 51(3): p. 300-6.

14.          Serpytis, M. and J. Ivaskevicius, The influence of fluid balance on intra-abdominal pressure after major abdominal surgery. Medicina (Kaunas), 2008. 44(6): p. 421-7.

15.          Ivatury, R.R., et al., Intra-abdominal hypertension after life-threatening penetrating abdominal trauma: prophylaxis, incidence, and clinical relevance to gastric mucosal pH and abdominal compartment syndrome. J Trauma, 1998. 44(6): p. 1016-21.

16.          Joseph, D.K., et al., Decompressive laparotomy to treat intractable intracranial hypertension after traumatic brain injury. J Trauma, 2004. 57(4): p. 687-95.

17.     Oda, S., et al., Management of Intra-abdominal Hypertension in Patients With Severe Acute Pancreatitis With Continuous Hemodiafiltration Using a Polymethyl Methacrylate Membrane Hemofilter. Ther Apher Dial, 2005. 9(4): p. 355-61.

18.     Sun, Z.X., H.R. Huang, and H. Zhou, Indwelling catheter and conservative measures in the treatment of abdominal compartment syndrome in fulminant acute pancreatitis. World J Gastroenterol, 2006. 12(31): p. 5068-70.

19.          Cheatham, M.L. and K. Safcsak, Is the evolving management of intra-abdominal hypertension and abdominal compartment syndrome improving survival? Crit Care Med, 2010. 38(2): p. 402-7.

20.     Ennis, J.L., et al., Joint Theater Trauma System implementation of burn resuscitation guidelines improves outcomes in severely burned military casualties. J Trauma, 2008. 64(2 Suppl): p. S146-51; discussion S151-2.

21.          Batacchi, S., et al., Vacuum-assisted closure device enhances recovery of critically ill patients following emergency surgical procedures. Crit Care, 2009. 13(6): p. R194.

22.          Kimball, E.J., et al., A prospective evaluation of the protocolized managment of intra-abdominal hypertension and the abdominal compartment syndrome. Acta Clinica Belgica, 2009. 64(3): p. 272 - Abstract 110.

23.          Rasmussen, T.E., et al., Early abdominal closure with mesh reduces multiple organ failure after ruptured abdominal aortic aneurysm repair: guidelines from a 10-year case-control study. J Vasc Surg, 2002. 35(2): p. 246-53.

24.     Tao, J., et al., Diagnosis and management of severe acute pancreatitis complicated with abdominal compartment syndrome. J Huazhong Univ Sci Technolog Med Sci, 2003. 23(4): p. 399-402.

25.          Raeburn, C.D., et al., The abdominal compartment syndrome is a morbid complication of postinjury damage control surgery. Am J Surg, 2001. 182(6): p. 542-6.

26.     Ejike, J.C. and M. Mathur, Occurrence and outcome of abdominal compartment syndrome in critically ill children. Critical Care Medicine, 2005. 33(12 supplement): p. A95, Abstract 158-M.

27.        Cipolla, J., et al., A proposed algorithm for managing the open abdomen. Am Surg, 2005. 71(3): p. 202-7.

28.        Reintam, A., et al., Impact of abdominal pressure on ICU mortality. Intensive Care Medicine, 2005. 31, Supplement 1(134): p. S8-Abstract 014.

29.        Kimball, E.J., et al., Cost savings after implementation of an IAH/ACS management protocol. Am Surg, 2011. 77(7): p. S113.

30.     Cheatham, M., K. Safcsak, and M. Sugrue, Long-term implications of Intra-abdominal hypertension and abdominal compartment syndrome: Physical, Mental and financial. Am Surg, 2011. 77(7): p. S78-S82.

31.    Kaplan, M.J., et al., Does the method of temporary abdominal closure affect outcomes in trauma patients managed with an open abdomen? Am Surg, 2011. 77(7): p. S112.

32.     Du, X.J., et al., Hydroxyethyl Starch Resuscitation Reduces the Risk of Intra-Abdominal Hypertension in Severe Acute Pancreatitis. Pancreas, 2011.

33.     Cheatham, M.L. and K. Safcsak, Percutaneous Catheter Decompression in the Treatment of Elevated Intra-abdominal Pressure. Chest, 2011.