News on intra-abdominal hypertension – focus on fluids and hemodynamics

Conflicts of interest World Society of the Abdominal Compartment Syndrome Secretary – Inneke De laet President – Jan De Waele

Fluids and intra-abdominal pressure (IAP): what’s new? Inneke De laet ZNA Stuivenberg

What is IAP? Definitions Entity Definition Intra-abdominal pressure (IAP) IAP is the steady-state pressure concealed within the abdominal cavity Intra-abdominal hypertension (IAH) IAH is defined by a sustained or repeated pathological elevation in IAP ≥ 12mmHg Abdominal compartment syndrome (ACS) ACS is defined as a sustained IAP > 20mmHg (with or without an APP < 60mmHg) that is associated with new organ dysfunction/ failure. Primary IAH/ACS Primary ACS is a condition associated with injury or disease in the abdominopelvic region that frequently requires early surgical or interventional radiological intervention Secondary IAH/ACS Secondary ACS refers to conditions that do not originate from the abdominopelvic region Recurrent IAH/ACS Recurrent ACS refers to the condition in which ACS redevelops following previous surgical or medical treatment of primary or secondary ACS

Effect on organ function CNS: ICP CPP Pulmonary: intrathoracic pressure  PIP  Paw  Cdyn  paO2  paCO2  Qs/Qt  Vd/Vt  Cardiac: CVP PCWP SVR CO venous return HR= MAP= IAH Hepatic: portal blood flow  lactate clearance  mitochondrial function  Renal: diuresis  renal blood flow  RVR  GFR  Visceral: Feeding intolerance  SMA blood flow  mucosal blood flow  pHi  Abdominal Wall: compliance  rectus sheath blood flow 

IAP is associated with mortality Prospective observational study in mechanically ventilated mixed ICU patients OBJECTIVE: To investigate the differences in incidence, time course and outcome of primary versus secondary intra-abdominal hypertension (IAH), and to evaluate IAH as an independent risk factor of mortality in a presumable risk population of critically ill patients. DESIGN: Prospective observational study. SETTING: General intensive care unit of a university hospital. PATIENTS: A total of 257 mechanically ventilated patients at presumable risk for the development of IAH were studied during their ICU stay and followed up for 90-day survival. INTERVENTIONS: Repeated measurements of intra-abdominal pressure (IAP). MEASUREMENTS AND RESULTS: IAP was measured intermittently, via bladder. IAH (sustained or repeated IAP > or = 12 mmHg) developed in 95 patients (37.0%). Primary IAH was observed in 60 and secondary IAH in 35 patients. Patients with secondary IAH demonstrated a significant increase of mean IAP during the first three days (mean DeltaIAP was 2.2 +/- 4.7 mmHg), whilst IAP decreased (mean DeltaIAP -1.1 +/- 3.7 mmHg) in the patients with primary IAH. The patients with IAH had a significantly higher ICU- (37.9 vs. 19.1%; P = 0.001), 28-day (48.4 vs. 27.8%, P = 0.001), and 90-day mortality (53.7 vs. 35.8%, P = 0.004) compared to the patients without the syndrome. Patients with secondary IAH had a significantly higher ICU mortality than patients with primary IAH (P = 0.032). Development of IAH was identified as an independent risk factor for death (OR 2.52; 95% CI 1.23-5.14). CONCLUSIONS: Secondary IAH is less frequent, has a different time course and worse outcome than primary IAH. Development of IAH during ICU period is an independent risk factor for death. Reintam A et al., Intensive Care Med 2008, 34: 1624-31.

Relationship fluids and IAP Conclusions: Among mixed ICU patients, … and the volume of crystalloids used in their initial resuscitation appear to be important considerations in determining risk of IAH/ACS Risk factors for IAH … among mixed ICU patients included obesity, sepsis, abdominal surgery, ileus development and fluid resuscitation. INTRODUCTION: Although intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are associated with substantial morbidity and mortality among critically ill adults, it remains unknown if prevention or treatment of these conditions improves patient outcomes. We sought to identify evidence-based risk factors for IAH and ACS in order to guide identification of the source population for future IAH/ACS treatment trials and to stratify patients into risk groups based on prognosis. METHODS: We searched electronic bibliographic databases (MEDLINE, EMBASE, PubMed, and the Cochrane Database from 1950 until January 21, 2013) and reference lists of included articles for observational studies reporting risk factors for IAH or ACS among adult ICU patients. Identified risk factors were summarized using formal narrative synthesis techniques alongside a random effects meta-analysis. RESULTS: Among 1224 citations identified, 14 studies enrolling 2500 patients were included. The 38 identified risk factors for IAH and 24 for ACS could be clustered into 3 themes and 8 subthemes. Large volume crystalloid resuscitation, the respiratory status of the patient, and shock/hypotension were common risk factors for IAH and ACS that transcended across presenting patient populations. Risk factors with pooled evidence supporting an increased risk for IAH among mixed ICU patients included obesity [4 studies; odds ratio (OR) 5.10; 95% confidence interval (CI), 1.92 to 13.58], sepsis (2 studies; OR 2.38; 95% CI, 1.34 to 4.23), abdominal surgery (4 studies; OR 1.93; 95% CI, 1.30 to 2.85), ileus (2 studies; OR 2.05; 95% CI, 1.40 to 2.98), and large volume fluid resuscitation (2 studies; OR 2.17; 95% CI, 1.30 to 3.63). Among trauma and surgical patients, large volume crystalloid resuscitation and markers of shock/hypotension and metabolic derangement/organ failure were risk factors for IAH and ACS while increased disease severity scores and elevated creatinine were risk factors for ACS in severe acute pancreatitis patients. CONCLUSIONS: Although several IAH/ACS risk factors transcend across presenting patient diagnoses, some appear specific to the population under study. As our findings were somewhat limited by included study methodology, the risk factors reported in this study should be considered candidate risk factors until confirmed by a large prospective multi-centre observational study.

WSACS medical management algorithm www.wsacs.org

Determine which mechanism(s) is/are most likely to benefit the patient Evacuating intraluminal contents Evacuating extraluminal contents Improving abdominal compliance Controlling fluid balance Optimizing systemic /regional perfusion Determine which mechanism(s) is/are most likely to benefit the patient Patient develops IAH (IAP>12mmHg)

Determine which mechanism(s) is/are most likely to benefit the patient Evacuating intraluminal contents Evacuating extraluminal contents Improving abdominal compliance Controlling fluid balance Optimizing systemic /regional perfusion Determine which mechanism(s) is/are most likely to benefit the patient Patient develops IAH (IAP>12mmHg)

How to deal with IAP and fluids Goals To ensure adequate tissue perfusion and oxygenation To limit the amount of crystalloid resuscitation To remove excess fluids from the body Techniques Goal directed resuscitation? Colloids? Hypertonic solutions? Diuretics? Ultrafiltration?

Limiting crystalloid resuscitation

Colloids to reduce fluid requirement? Some data in patients with SAP, e.g. Retrospective analysis of 47 patients with SAP 3 groups: Low ratio group: crystalloid colloid ratio of <1,5 Middle ratio group: crystalloid colloid ratio of 1,5-3 High ratio group: crystalloid colloid ratio of >3 OBJECTIVE: To investigate the impact of fluid resuscitation with different ratio of crystalloid-colloid in early resuscitation stage on prognosis of patients with severe acute pancreatitis (SAP). METHODS: A retrospective analysis was made by reviewing clinical data of 47 patients with SAP from January 2001 to December 2011. According to crystalloid-colloid ratio 1.5 or 3, which was the input volume of crystalloid fluid versus colloid fluid in the first 24 hours, patients were divided into low ratio group (crystalloid-colloid ratio <1.5, n=13), middle ratio group (crystalloid-colloid ratio 1.5-3, n=15) and high ratio group (crystalloid-colloid ratio >3, n=19). Among the patients who had been successfully resuscitated, rate of mechanical ventilation, the oxygenation index, intra-abdominal pressure (IAP), and the amount of fluid retention in the third space within the first 24 hours, as well as the parameters of fluid resuscitation and the survival rate within 2 weeks were collected and analyzed. RESULTS: (1) In the first 24 hours, the rate of mechanical ventilation in the high ratio group was significantly higher than that in the middle ratio group and the low ratio group (68.4% vs. 20.0%, 23.1%, both P<0.05); the oxygenation index was significantly lower than that in the middle ratio group and in the low ratio group (180.7+/-26.3 mm Hg vs. 280.6+/-24.8 mm Hg, 260.3+/-25.7 mm Hg, both P<0.05); the IAP was significantly higher than that in the middle ratio group and the low ratio group (16.8+/-3.6 cm H(2)O vs. 13.4+/-3.5 cm H(2)O, 13.1+/-3.3 cm H(2)O, both P<0.05); the amount of fluid retention in the third space was significant higher than that in the middle ratio group and the low ratio group (2834+/-631 ml vs. 1887+/-282 ml, 1865+/-300 ml, both P<0.05). There was no significant difference in above indexes between middle ratio group and low ratio group (all P>0.05). (2) In the first 24 hours, the volume of crystalloid in high ratio group was significantly larger than that in the middle ratio group and the low ratio group (3611+/-798 ml vs. 2308+/-416 ml, 2124+/-477 ml, both P<0.05); and the volume of colloid in high ratio group and middle ratio group was significantly lower than that in the low ratio group (993+/-233 ml, 948+/-140 ml vs. 1506+/-332 ml, both P<0.05); and the mean crystalloid-colloid rate in the high ratio group was significantly higher than that in the middle ratio group and the low ratio group (3.65+/-0.13 vs. 2.43+/-0.13, 1.41+/-0.08, both P<0.05). The volume of infused fluid during the first 72 hours in the high ratio group was significantly higher than that in the middle and low ratio groups (11 941+/-1161 ml vs. 9036+/-982 ml, 9400+/-1051 ml, both P<0.05). (3) The survival rate in the high ratio group (36.8%) was significantly lower than that in the middle ratio group (86.7%, P<0.05) and the low ratio group (61.5%, P>0.05). CONCLUSIONS: A suitable crystalloid-colloid ratio should be considered in the early stage of resuscitation in patients with severe acute pancreatitis, which would result in a decrease in the fluid retention in the third space as well as an improvement of survival rate in return. It is suggested that the middle ratio of crystalloid-colloid fluid resuscitation should be the optimal strategy. Chang YS et al. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2013 Jan: 25(1): 48-51

Choice of fluids: colloids Low ratio Middle ratio High ratio Number of patients 13 15 19 Mechanical ventilation after 24h (%) 23,1 20.0 68.0* PaO2/FiO2 (mmHg) 260.3+/-25.7 280.6+/-24.8 180.7+/-26.3* IAP (mmHg) 13.1+/-3.3 13.4+/-3.5 16.8+/-3.6* Fluid retention (mL) 1865+/-300 1887+/-282 2834+/-631* Crystalloid volume in 24h (mL) 2124+/-477 2308+/-416 3611+/-798* Volume infused/72h (mL) 9400+/-1051 9036+/-982 11 941+/-1161* 28d Survival (%) 61.5 86,7 36.8* *: statistically significant Chang YS et al. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2013 Jan: 25(1): 48-51

Choice of fluids: colloids Low ratio Middle ratio High ratio Number of patients 13 15 19 Mechanical ventilation after 24h (%) 23,1 20.0 68.0* PaO2/FiO2 (mmHg) 260.3+/-25.7 280.6+/-24.8 180.7+/-26.3* IAP (mmHg) 13.1+/-3.3 13.4+/-3.5 16.8+/-3.6* Fluid retention (mL) 1865+/-300 1887+/-282 2834+/-631* Crystalloid volume in 24h (mL) 2124+/-477 2308+/-416 3611+/-798* Volume infused/72h (mL) 9400+/-1051 9036+/-982 11 941+/-1161* 28d Survival (%) 61.5 86,7 36.8* *: statistically significant Chang YS et al. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2013 Jan: 25(1): 48-51

Colloids to reduce fluid requirement? Too many data about adverse outcomes with synthetic colloids Adverse effects of excessive crystalloid resuscitation are well documtented There seems to be a need for a solution with colloid properties without the complications So, back to the natural colloids (plasma, albumin)?

Plasma: the “new” colloid? Crystalloid Plasma p-value Nr of patients 15 16 Volume perfused (24h) 22.1 ± 12.8 12.3 ± 9.3 0.02 Urine output (mL/kg/h) 0.77 ± 0.21 0.76 ± 0.33 0.6 Admission IAP (mmHg) 5.9 ± 2.7 5.9 ± 3.5 0.95 Peak IAP (mmHg) 32.5 ± 9.5 16.4 ± 7.4 <0.0001 Peak creatinine (mg/dL) 1.90 ± 1.00 1.48 ± 0.92 0.23 Base excess/deficit -1.7 ± 5.5 1.2 ± 3.2 0.07 BACKGROUND: The volume of resuscitation in burn patients has been shown to correlate with intra-abdominal pressure (IAP). Limiting volume may reduce consequences of IAP and abdominal compartment syndrome. Colloid resuscitation has been previously shown to limit the volume required initially after burn. METHODS: Thirty-one patients were prospectively followed. Inclusion criteria were a burn of 25% total body surface area with inhalation injury or 40% total body surface area without. Patients received crystalloid (Parkland formula) or plasma resuscitation. IAP was measured by means of urinary bladder transduction. RESULTS: Mean age, area of burn, and baseline IAP were not different. Urine output was maintained. There was a greater increase in IAP with crystalloid (26.5 vs. 10.6 mmHg, p < 0.0001). Two patients in the plasma group developed IAP greater than 25 mmHg; only one patient in the crystalloid group maintained IAP less than 25 mmHg. More fluid volume was required with crystalloid resuscitation, 0.26 L/kg, versus 0.21 L/kg (p < 0.005). Correlation was seen in both groups between volume of fluid and IAP (crystalloid, r = 0.351; plasma, r = 0.657; all patients, r = 0.621). CONCLUSION: Plasma-resuscitated patients maintained an IAP below the threshold of complications of intra-abdominal hypertension. This appears to be a direct result of the decrease in volume required. Lower fluid volume regimens should be given consideration as the incidence and consequences of intra-abdominal hypertension in burn patients continue to be defined. O'Mara MS et al, J Trauma 2005, 58(5):1011-1018.

Choice of fluids: plasma? RCT in patients with SAP comparing 3 fluid regimens: Control group: Ringer’s lactate + HES (2:1), routine resuscitation EGDT 1 group: Ringer’s lactate + HES, EGDT (CVP, MAP, diuresis, ScvO2 or SvO2) EGDT 2 group: Ringer’s lactate, HES, 2 units of FFP daily for 3 days, EGDT n=200 Results: Wang MD et al. Chin Med J (Engl) 2013 May: 126(10): 1987-8

Choice of fluids: plasma? Wang MD et al. Chin Med J (Engl) 2013 May: 126(10): 1987-8

Choice of fluids: plasma? Secondary outcomes: Ventilation days: control > EGDT 1 > EGDT 2 ICU length of stay: control > EGDT 1 > EGDT 2 Fluid resuscitation: control = EGDT 1 > EGDT 2 Cumulative fluid balance: control = EGDT 1 > EGDT 2 Negative fluid balance on day 3 was achieved only in the EGDT 2 group

Use of plasma as a colloid Pro: Should avoid complications associated with synthetic molecules May be biologically active Con: Expensive Limited availability May be biologically active (possibility of immunologic complications, inflammatory complications, TRALI, TEE…)

Use of albumin to limit crystalloids Only 1 retrospective study on PAL treatment No prospective data in resuscitation settings incorporating IAP Surviving Sepsis Campaign Guidelines 2013: “we suggest the use of albumin in the resuscitation of severe sepsis and septic shock when patients require substantial amounts of crystalloids.” Controversy remains about methodology of studies supporting these recommendations

Removing excess fluid

Conservative fluid strategies seem to impact outcome BACKGROUND: Recent studies have suggested that early goal-directed resuscitation of patients with septic shock and conservative fluid management of patients with acute lung injury (ALI) can improve outcomes. Because these may be seen as potentially conflicting practices, we set out to determine the influence of fluid management on the outcomes of patients with septic shock complicated by ALI. METHODS: A retrospective analysis was performed at Barnes-Jewish Hospital (St. Louis, MO) and in the medical ICU of Mayo Medical Center (Rochester, MN). Patients hospitalized with septic shock were enrolled into the study if they met the American-European Consensus definition of ALI within 72 h of septic shock onset. Adequate initial fluid resuscitation (AIFR) was defined as the administration of an initial fluid bolus of >or= 20 mL/kg prior to and achievement of a central venous pressure of >or= 8 mm Hg within 6 h after the onset of therapy with vasopressors. Conservative late fluid management (CLFM) was defined as even-to-negative fluid balance measured on at least 2 consecutive days during the first 7 days after septic shock onset. RESULTS: The study cohort was made up of 212 patients with ALI complicating septic shock. Hospital mortality was statistically lowest for those achieving both AIFR and CLFM and higher for those achieving only CLFM, those achieving only AIFR, and those achieving neither (17 of 93 patients [18.3%] vs 13 of 31 patients [41.9%] vs 30 of 53 patients [56.6%] vs 27 of 35 [77.1%], respectively; p < 0.001). CONCLUSIONS: Both early and late fluid management of septic shock complicated by ALI can influence patient outcomes. Murphy et al, Chest 2009: 136B(1): 102-109

Can diuretics be used? Pro: Questions: Can achieve fluid removal Renal function? Will injured kidney(s) respond? Haemodynamic tolerance?

Works in ADHF Mullens et al, J Am Coll Card 2008; 51 (3): 300-306

PAL treatment Hypothesis: Combined therapy with PEEP, albumin and frusemide Should mobilize interstitial fluid to the vascular compartment and evacuate fluids through diuresis Retrospective matched control case series (n=114) INTRODUCTION: Achievement of a negative fluid balance in patients with capillary leak is associated with improved outcome. We investigated the effects of a multi-modal restrictive fluid strategy aiming for negative fluid balance in patients with acute lung injury (ALI). METHODS: In this retrospective matched case-control study, we included 114 mechanically ventilated (MV) patients with ALI. We compared outcomes between a group of 57 patients receiving PAL-treatment (PAL group) and a matched control group, abstracted from a historical cohort. PAL-treatment combines high levels of positive end-expiratory pressure, small volume resuscitation with hyperoncotic albumin, and fluid removal with furosemide (Lasix(R)) or ultrafiltration. Effects on extravascular lung water index (EVLWI), intra-abdominal pressure (IAP), organ function, and vasopressor therapy were recorded during 1 week. The primary outcome parameter was 28-day mortality. RESULTS: At baseline, no significant intergroup differences were found, except for lower PaO2/FIO2 and increased IAP in the PAL group (174.5 +/- 84.5 vs 256.5 +/- 152.7, p = 0.001; 10.0 +/- 4.2 vs 8.0 +/- 3.7 mmHg, p = 0.013, respectively). After 1 week, PAL-treated patients had a greater reduction of EVLWI, IAP, and cumulative fluid balance (-4.2 +/- 5.6 vs -1.1 +/- 3.7 mL/kg, p = 0.006; -0.4 +/- 3.6 vs 1.8 +/- 3.8 mmHg, p = 0.007; -1,451 +/- 7,761 vs 8,027 +/- 5,254 mL, p < 0.001). Repercussions on cardiovascular and renal function were limited. PAL-treated patients required fewer days of intensive care unit admission and days on MV (23.6 +/- 15 vs 37.1 +/- 19.9 days, p = 0.006; 14.6 +/- 10.7 vs 25.5 +/- 20.2 days, respectively) and had a lower 28-day mortality (28.1% vs 49.1%, p = 0.034). CONCLUSION: PAL-treatment in patients with ALI is associated with a negative fluid balance, a reduction of EVLWI and IAP, and improved clinical outcomes without compromising organ function.

Baseline characteristics Control group PAL group P-value APACHE II 22.7 ± 11.1 22.9 ± 11.4 0.934 PaO2/FiO2 ratio (mmHg) 256.5 ± 152.7 174.5 ± 84.5 0.001 IAP (mmHg) 8.0 ± 3.7 10.0 ± 4.2 0.013 Results -123 ± 166.4 99.9 ± 110.5 <0.001 Change in IAP (mmHg) 1.8 ± 3.8 -0.4 ± 3.6 0.007 Cumulative fluid balance (L) 8027 ± 5254 -1451 ± 7761 EVLWI (mL/kg) -1.1 ± 3.7 -4.2 ± 5.6 0.006 Serum creatinine (mg/dL) -0.5 ± 2.0 -0.1 ± 1.1 0.171 SOFA cardiovascular -0.5 ± 1.9 -1.2 ± 2.0 0.087

PAL treatment and outcome Cordemans C et al. Ann Intens Care 2012, 2(Suppl 1): S15

BUMIAP study Retrospective study on all patients receiving loop diuretics while monitoring IAP (Ghent University Hospital) Number of patients /patient days 266 / 869 Age 60.2 ± 15.4 years APACHE II score 22.2 ± 7.3 IAP 13.2 ± 4.0 mmHg Fluid balance after 1 day of bumetanide +1509 ± 1938 mL Patients with/without IAH 62.3 / 48.4 %

In patients with IAH and negative fluid balance, IAP was significantly decreased after 24h of bumetanide (difference -1.32mmHg ± 0.50, p<0.001)

Alternative: ultrafiltration Pro: Can be applied in patients with AKI Can achieve fluid removal Con: Hemodynamic consequences? Adverse effect on renal function or renal recovery? Riisk of catheter related and RRT related complications

If the diuretics don’t work Mullens et al. J Card Fail 2008; 14 (6): 508-514

CRRT: some small reports Fluid balance (L) -0.4 -4.4 -6.2 +.6 -0.9 -2.1 -4.8 Kula et al.Intens Care Med 2004; 30: 2138-2139

Conclusions Crystalloid fluid resuscitation is the most important risk factor for secondary IAH/ACS Secondary IAH/ACS carries a high morbidity and mortality We need better fluid strategies to limit the amount of crystalloid resuscitation We need prospective studies on albumin (and plasma?) used as add-on resuscitation for patients with distributive shock requiring large amounts of crystalloids