Vasopressin Versus Vasopressin Analogues in Septic Shock

A 52 year old female was admitted to the ICU with septic shock secondary to cholangitis. She had liver cirrhosis secondary to alcoholic liver disease, although she had been abstinent since an admission with acute alcoholic hepatitis  2 years previously. She had recently entered the assessment pathway for orthotopic liver transplantation.

She presented to the Emergency Department with a short history of fever and confusion and falls. She was pyrexial, tachycardic and hypotensive. Her inflammatory markers were elevated and her liver enzyme profile suggested cholestasis. There were no other localising features on examination or preliminary investigation.

She was commenced in the ED on broad-spectrum antibiotic therapy (piperacillin-tazobactam) and fluid resuscitation consisting of Hartmann’s solution and 4% human albumin solution. Her blood pressure remained labile throughout the early part of her admission. She fulfilled the criteria for septic shock with evidence of evolving multi-organ dysfunction.

 

The patient received early, aggressive multi-organ support. Tracheal intubation and pressure-controlled ventilation were instituted due to grade III/ IV encephalopathy and a high work of breathing in response to profound metabolic acidaemia. A thorough clinical assessment of intravascular volume status was conducted, suggesting that the patient was adequately filled. Vasopressor therapy was initiated using noradrenaline to achieve a target MAP of 65mmHg. CVVHDF was commenced to control the severe acidaemia and hyperlactataemia.

The patient was vasoplegic and remained profoundly hypotensive despite rapidly escalating doses of noradrenaline and the addition of hydrocortisone. Continued assessment of intravascular status confirmed adequate filling and cardiac output monitoring using a pulse-contour analysis system confirmed a low SVRI- high cardiac output state.  Her noradrenaline requirements soon exceeded 0.4mcg/kg/min-1, at this point a vasopressin infusion was introduced at 0.03units/hr-1. This was associated with an improvement in haemodynamic indices; the target MAP was achieved and thereafter remained stable with a slow reduction in noradrenaline requirement. On day 2 the continuous vasopressin infusion was converted to terlipressin by bolus dose regime (2mg QDS).

An urgent ultrasound scan of her biliary system revealed an obstructed common bile duct which was treated by percutaneous biliary drainage. An Enterococcus was isolated from drain fluid and blood cultures within 48 hours and antibiotic therapy tailored accordingly. The patient was weaned from organ support and discharged to the hepatology unit 9 days after admission.

What is the rationale for the use of vasopressin in septic shock? Are vasopressin analogues as effective?Read More »

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Intra-Abdominal Hypertension

 

A 48 year old male was admitted to the ICU with rapidly evolving multi-organ dysfunction. He was in type I respiratory failure, hypotensive and had stage II acute kidney injury. He had been an inpatient recovering from a laparotomy for major urological surgery 5 days prior to his ICU admission. This was complicated by a major intraoperative haemorrhage.

The patient was commenced on treatment for presumed hospital acquired pneumonia. He was placed on mechanical ventilation and a noradrenaline infusion was commenced to maintain a mean arterial pressure of ≥65mmHg. Over the following 24 hours the patient displayed worsening lung compliance in the context of adequate oxygenation and an atracurium infusion was started. Simultaneously the patient appeared to develop an ileus and he became anuric. Repeated clinical examination revealed an increasingly distended abdomen. A CT of the abdomen and pelvis showed a large left sided retroperitoneal haematoma with evidence of pelvico-ureteric leak on the left and an associated fluid collection. The patient was taken to theatre for urgent re-laparotomy.

At the conclusion of the operation, the surgical team was unable to close the abdomen due to significant bowel oedema. They accepted a laparostomy and returned the patient to ICU with a negative pressure wound dressing in-situ. Post-operatively, there was significant improvement in lung compliance, vasopressor requirement and urine output. Enteral feeding was quickly re-established. The abdomen was closed during the same hospital admission and the patient survived-to-discharge home. At no point was this patient’s intra-abdominal pressure measured.

 

Describe the management of intra-abdominal hypertension.

Christopher Westall

Intra-abdominal hypertension (IAH)- abdominal compartment syndrome (ACS) is a well-recognised cause of morbidity and mortality in critically ill patients, rising to prominence in the 1990s with increased early survival of patients with intra-abdominal pathology requiring emergent laparotomy (principally abdominal aortic aneurysm repair and blunt trauma).1,2 IAH/ ACS may be precipitated by a range of insults local (primary IAH) and distant (secondary IAH) to the abdomen.3 The syndrome encompasses a spectrum of severity and there are a range of treatment options, though with little high quality evidence to support these.

The World Society of the Abdominal Compartment Syndrome (WSACS) consensus guidelines recommend that intra-abdominal pressure (IAP) is measured using the trans-bladder technique in any critically ill patient with an associated risk factor for IAH. The normal value for IAP is <12mmHg. IAH is then categorized by increasing pressure increments from grade I (IAP 12-15mmHg) to grade IV (>25mmHg). Abdominal compartment syndrome is defined as sustained IAP >20mmHg associated with new organ dysfunction.3

The WSACS Consensus proposes a management algorithm for IAH/ ACS that is loosely analogous to commonly encountered algorithms for managing raised intracranial pressure The abdomen is considered a fixed compartment with intra-luminal and extra-luminal volumes that can be manipulated through neutral-negative fluid balance, nasogastric and colonic decompression and percutaneous drainage of ascites/collections. In this instance, however, the compliance of the “box”, the abdominal wall, can also be manipulated by patient position, ventilatory strategy and neuromuscular blockade. Decompressive [laparotomy] therapy is reserved for algorithm failure.

The efficacy of protocolised management of IAH/ACS has never been demonstrated. A single prospective observational study suggested reduction in morbidity and mortality using algorithm based management of IAH; the authors quoted an increase in survival-to-discharge rate from 50 to 72% (p= 0.015) across 6 years with improved rates of same-admission closure. However the study was single centre, recruiting patients only after the laparostomy, with substantial selection and observer bias. Furthermore it was unclear which parts of the protocol were effective.4 While the basic principles underlying the WCASC 2013 algorithm are sensible, it must be acknowledged that proposed therapies such as resuscitation with hypertonic fluids, diuretic-driven diuresis and ultrafiltration through renal replacement therapies have no evidence to support them and have potentially serious implications for the patient.

Given that the efficacy of protocolised management of IAH/ACS is uncertain, is there then any evidence to support the measurement of IAP in every “at risk” patient, especially since the list of risk factors for IAH is so extensive that it is difficult to imagine a critically ill patient that is not at risk. This would not be without significant task-burden to critical care nursing staff, and as with any clinical index in ICU, risks morbidity from misinterpretation. There are only two small studies that have examined whether clinical examination can reliably predict intra-abdominal pressure; both small studies with significant methodological flaws and both conducted between 1996- 2000 when awareness of IAH was comparatively low. Importantly both studies compared examination to IAP measurement at pressures well below 20mmHg, where there is little evidence that specific intervention improves patient outcome, beyond highlighting that that patient is at risk of ACS.5,6

Decompressive laparotomy is recommended for the treatment of all patients with ACS refractory to medical therapy.3 In modern practice it is difficult to accurately assess the performance of this strategy in primary IAH/ACS, such is the absence of clinical equipoise. As many reviews acknowledge, the improvement in patient survival rates associated with primary laparostomy in abdominal trauma patients in the 1990s caused a fundamental paradigm shift from which it is now difficult to ethically justify alternative treatment strategies.1,2 That is to say that many patients with IAH/ ACS will now present to the ICU once decompressive laparostomy has either occurred or is imminently planned.

The benefits of decompressive laparotomy in secondary ACS are certainly less; data exists only for acute severe pancreatitis and sepsis associated with secondary peritonitis. While in both instances it must be acknowledged that laparostomy reduces IAP, like many interventions in a critically ill patient population, this does not translate into mortality benefit.7,8 As commentators note, laparostomy may often be performed because of a conceptual benefit of relook-laparotomy 48 hours later, rather than inability to close the abdomen or specific concerns regarding ACS.2 Indeed, regarding secondary peritonitis, there is good evidence that primary closure with on-demand re-laparotomy is non-inferior to laparostomy and planned re-laparotomy, and is associated with fewer surgeries and lower healthcare costs.9 This strategy is now [weakly] endorsed by the WCACS.3

One point that is widely agreed upon is the management of laparostomy. It appears universally agreed that negative pressure wound therapy (NPWT, i.e. “vac dressings”), with or without a form of dynamic retention system, is superior to previously popular methods such as bioprosthetic mesh and Bogota bag. The largest systematic review on the subject suggests that NPWT is associated with improved rates of primary delayed fascial closure (57.8%, 95% CI 50.8- 64.7) and mortality (22.3%, 95% CI 17.5- 27.5) with lower rates of entero-atmospheric fistulation (7.0%, 95% CI 5.0- 9.3) and abscess formation (4.2%, 95% CI 2.3- 6.9).10 This systematic review heavily influenced the most recent NICE review on the topic leading to endorsement of NPWT in clinical guideline IPG467, “Negative pressure wound therapy for the open abdomen” (2013).


Conclusion

The measurement of IAP in all at-risk critically ill patients is probably unnecessary and burdensome in resource terms. Critical care practitioners should have a low index of suspicion for ACS in their patients; if this develops then decompressive laparotomy is the treatment of choice (unless there is a large extra-luminal collection amenable to urgent drainage), particularly since modern laparostomy management appears to be associated with an increasingly low complication rate, if the abdomen cannot be closed.

The consensus guidelines for IAH/ACS remind us that attention to detail; such as ensuring that enteral nutrition is succeeding, that bowel care is optimal and that fluid balance is tightly controlled, may prevent numerous serious ICU-associated syndromes from ever developing.


References

1. Balogh ZJ, Lumsdaine W, Moore EE, Moore FA. Postinjury abdominal compartment syndrome: from recognition to prevention. Lancet,  2014; 384:1466-75

2. Leppaniemi AK. Laparostomy: why and when? Critical Care 2010; 14: 216. DOI: 10.1186/cc8857

3. Kirkpatrick AW, Roberts DJ, De Waele J, Jaeschke R, Malbrain MLNG, De Keulenaer B, Duchesne J, Bjorck M, Leppaniemi A, Ejike JC, Sugrue M, et al.  Intra-abdominal compartment syndrome: updated consensus definitions and clinical practice guidelines from the World Society of the Abdominal Compartment Syndrome. Intensive Care Med, 2013; 39:1190-1206

4. Cheatham ML, Safcsak KRN. Is the evolving management of intra-abdominal hypertension and abdominal compartment syndrome improving survival? Crit Care Med,  2010; 38:402-407

5. Kirkpatrick AW, Brenneman FD, McLean RF, Rapanos T, Boulanger BR. Is clinical examination an accurate indicator of raised intra-abdominal pressure in critically injured patients? Can J Surg, 2000:43:207-11

6. Sugrue M, Bauman A, Jones F, Bishop G, Flabouris A, Parr M, Stewart A, Hillman K, Deane SA. Clinical examination is an inaccurate predictor of intra-abdominal pressure. World J Surg, 2002; 26:1428-31

7. Mentula P, Hienonen P, Kemppainen E, Puolakkainen P, Leppaniemi A. Surgical decompression for abdominal compartment syndrome in severe acute pancreatitis. Arch Surg, 2010; 145:764-9

8. Robledo FA, Luque-de-Leon E, Suarez R, Sanchez P, de la Fuente M, Vargas A, Mier J. Open versus closed management of the abdomen in the surgical treatment of severe secondary peritonitis: a randomized clinical trial. Surg Infect (Larchmt), 2007; 8:63–72

9. van Ruler O, Mahler CW, Boer KR, Reuland EA, Gooszen HG, Opmeer BC, de Graaf PW, Lamme B, Gerhards MF, Steller EP, van Till JW, et al. Comparison of on-demand vs planned relaparotomy strategy in patients with severe peritonitis: a randomized trial. JAMA, 2007; 298:865-73

10. Quyn AJ, Johnston C, Hall D, Chambers A, Arapova N, Ogston S, Amin AI. The open abdomen and temporary abdominal closure systems- historical evolution and systematic review. Colorectal Dis, 2012; 14: e429–38

 

Hyponatraemia and Renal Replacement Therapy

A 63 year old woman was admitted to the ICU from the Emergency Department with acute alcohol withdrawal, severe hyponatraemia (serum sodium level 114mmol/L), rhabdomyolysis (creatine kinase 46930u/L) and acute kidney injury (serum creatinine 262umol/L, urea 8.7mmol/L, potassium 4.6mmol/L, base excess -6.8 and anuric from the point of admission). Her corrected calcium level was 1.92mmol/L. She had been discovered on the floor at home after a presumed fall. It was unknown how long she had been on the floor, but there were extensive pressure injuries to the left elbow, buttocks and left leg. A CT scan of the brain had excluded significant acute intracranial pathology and a 12 lead ECG showed atrial fibrillation at a rate of 130 beats per minute.

The patient was intubated and mechanically ventilated to allow emergency treatment. She was sedated with remifentanil and propofol. Intravenous pabrinex and enteral chlordiazepoxide was given to treat her alcohol withdrawal, aiming for early extubation if possible. A low-dose noradrenaline infusion was required to maintain a mean arterial pressure ≥65mmHg. Calcium replacement was prescribed and full pressure relief measures were instituted. No specific treatment was given to rate control or cardiovert the patient.

The patient was clinically hypovolaemic, but since the duration of hyponatraemia was unknown (with suspicion of some chronicity related to alcohol dependence), aggressive fluid resuscitation was avoided. Continuous veno-veno haemodiafiltration (CVVHDF) was commenced using standard replacement fluid at a post-filter replacement rate of 10ml/kg/hr-1 and dialysate flow rate of 10ml/kg/hr-1 (blood pump at 200ml/hr). Concomitantly, a 5% dextrose infusion was administered; the rate of infusion and net fluid loss through ultrafiltration were adjusted constantly with a view to restoring euvolaemia over 24 hours while increasing serum sodium to a maximum level of 120mmol/L over the same time period. This strategy was continued the following day with a target sodium of 128mmol/L, thereafter tight control of sodium correction was relaxed.

She was extubated on day 3 and renal replacement was discontinued on day 4. The patient was discharged from ICU on day 6. At the point of discharge her serum sodium concentration was stable at 142mmol/L. She was neurologically intact.

What are the challenges in managing hyponatraemia in critically ill patients?Read More »

Decompressive Craniotomy in Traumatic Brain Injury

A 20 year-old man was admitted to his local district hospital with a severe head injury following an assault. On arrival in the Emergency Department he was agitated with a reduced conscious level, with evidence of blunt trauma to the head and neck. Prior to intubation, his Glasgow Coma Score (GCS) was recorded as 7 (E1V2M4), and with cervical spine precautions he underwent intubation with subsequent mechanical ventilation and sedation.

An urgent CT brain and cervical spine revealed early evidence of intracerebral contusions with diffuse areas of petechial intracerebral haemorrhage identified. Nasal and maxillary fractures were also seen, with no cervical spine pathology identified. He was transferred to the regional neurological centre for assessment and ongoing management.

On arrival in the Neurosurgical Intensive Care unit the patient underwent insertion of an intracranial pressure monitor revealing an intracranial pressure (ICP) of between 30-35 mmHg. Pupil reactivity was sluggish bilaterally. Sedation was changed to infusions of propofol, fentanyl and midazolam, positioning was optimised with 20 degree head-up tilt, endotracheal tube ties were replaced and targeted mechanical ventilation to EtCO2 4- 4.5kPa. Central venous access was established and an infusion of Noradrenaline was used to target cerebral perfusion pressure to 70mmHg.

Initial medical management stabilised ICP below 25mmHg, but within the next 12 hours this began to rise despite neuromuscular blockade and infusion of hypertonic saline. Further CT imaging revealed progression of the intracerebral contusions with developing oedema. The patient was transferred to the operating theatre for insertion of an external ventricular drain. CSF drainage resulted in an immediate but small improvement in ICP but again over the next 12 hours it began to rise, and decision was made for bifrontal decompressive craniectomy.

Subsequent recovery was slow and was complicated by ventilator-associated pneumonia, a protracted tracheostomy wean and severe agitation. The patient underwent intensive neuro-rehabilitation and had been decannulated, but was left with persistent cognitive impairment, seizures and depression.

What is the rationale for performing decompressive craniotomy in TBI?

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ICP Monitoring and Acute Liver Failure

ICP Monitoring and Acute Liver Failure

A 28-year-old lady presented to the medical team jaundiced with cramping upper abdominal pain and multiple episodes of vomiting over the previous day. She admitted ingesting Paracetamol 8 grams 3 days previously (staggered throughout the day) ostensibly to treat a frontal headache. She had been commenced on Citalopram 1 week previously for depression but denied taking any intentional overdose. On examination, she was slightly drowsy but GCS 15. HR 109, BP 136/92. Sats 98%on air. Her chest was clear, she was warm peripherally but jaundiced with some epigastric and RUQ tenderness on palpation. Her urine output was 10-20ml/hr.

Full Blood Count revealed Hb 152, WCC 24.7, Plats 301. She was in acute liver failure with Bil 189, AST 22970, ALT 13040, ALP 426 and coagulopathic with PT 82, APTT 72, Fib 0.7 Urea 5.7, Cr 193. Paracetamol and Salicylate were not detected. She was not acidotic with H+ 35, OCI2 3.7, pO2 17, Bic 20, BE –3. Lactate 7.1.

She was commenced on N-acetylcysteine and transferred to Critical Care. She was reviewed by the Hepatobiliary surgical team and placed on the super-urgent list for liver transplant. 

On Day 2, she became encephalopathic with GCS E3M5V5 and she was intubated and ventilated.Her PT had increased to 168 (INR >15) and she became anuric. She commenced FFP and Cryoprecipitate transfusions that improved her PT to 17, APTT 34 and Fibrinogen 1.5. An Intracranial Pressure (ICP) monitor was inserted and an opening pressure of 19mmHg was found. 2 hours post-insertion, it was noticed that her right pupil had increased in size from 2mm to 4mm and was poorly reactive. ICP remained at 16 and pCO2 4.1.

A brain CT showed a large haematoma in the right frontal region around the ICP bolt (which was not in the brain parenchyma but sitting in the skull) and mass effect with 5mm midline shift. There was also some lack of grey-white matter differentiation and sulcal effacement in keeping with diffuse oedema and mass effect.

INR was 1.7 and so further FFP was given. She was discussed with the neurosurgical registrar (in a separate hospital) who advised they would not drain at present but he would discuss with his Consultant and call back. 

Soon after, her right pupil increased to 8mm and the left to 7mm. Repeat CT brain showed slightly increased right frontal haematoma with 6mm midline shift and global oedematous cortical changes but no herniation. The ICP readings were thought to be inaccurate due to proximal placement and she was medically treated for raised ICP with hypertonic saline, mannitol and then therapeutic hypothermia. Despite this treatment, her pupils were fixed and dilated and so a thiopentone infusion was commenced.

The neurosurgeons advised that they would insert a further ICP monitor when INR <1.3 and so further FFP was given. An ICP bolt was inserted and the opening pressure was >120.

Discussions between the ICU, hepatobiliary and neurosurgical teams confirmed that she had a non-survivable injury and so this was discussed with her family. She was rewarmed, paralysis and then sedation were discontinued, brain stem death testing took place and she was extubated in the presence of her family. She died on Day 3 and was referred to the Coroner for further investigation.

What is the rationale for measuring ICP in acute liver failure?

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Scoring Systems for Acute Hepatic Dysfunction

Scoring Systems for Acute Hepatic Dysfunction

A 40 year old was admitted to hospital with his first presentation of alcoholic liver disease with symptoms of jaundice (bilirubin 248), poor mobility, hallucinations and passing of black stool. On admission to hospital, he was lethargic with features of Grade II encephalopathy, was coagulopathic (INR 3.1), had deranged electrolytes (sodium 114, potassium 2.9), but a normal creatinine (54) and a raised white cell count (15.9). He was haemodynamically stable and had a haemoglobin of 119g/L with no signs of active bleeding. His abdomen was distended (ascites), he was visibly jaundiced and had spider naevi on his chest. An abdominal ultrasound was performed that showed liver cirrhosis, borderline splenomegaly, small volume ascites and normal kidneys. A full liver screen revealed no infective cause and his AST:ALT ratio suggested alcoholic liver disease. His prognostic indicator scores were all suggestive of severe alcoholic liver hepatitis (Maddrey score: 131; Childs: C; Lille Score: 1; GAHS: 10; MELD: 29). His serum ammonia level was 170. He was commenced on terlipressin, prednisolone and pentoxyphylline and thiamine. Despite this, his encephalopathy progressed to grade 4 and he required intubation and ventilation for airway protection and a presumed aspiration pneumonia. His liver function and coagulopathy continued to worsen, and he developed an acute kidney injury necessitating commencement of renal replacement therapy. He required noradrenaline to support his blood pressure. Ascitic tap ruled out spontaneous bacterial peritonitis. He was discussed with regional liver centres, but was not felt to be a transplant candidate. His liver and renal function continued to deteriorate and eventually treatment was withdrawn nearly 3 weeks into his admission.

Describe the scoring systems for assessing the severity of acute hepatic dysfunction.

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Rapid Response Systems

Rapid Response Systems

An elderly man was admitted with an acute abdomen and free air visible under the diaphragm on CXR. He was fluid resuscitated before undergoing emergency laparotomy, where a perforated duodenal ulcer was oversewn. He was admitted to ICU postoperatively, extubated the next morning and deemed fit for discharge to the surgical ward later that day. Due to a lack of surgical beds, he was eventually discharged from ICU at 22:30. Eight hours post discharge, he was urgently re-referred to ICU after being found moribund on the ward. Before he could be seen and assessed he suffered an unrecoverable asystolic arrest. Review of his observation charts showed that there had been a clear deterioration in recorded observations, including hypotension for the two preceeding hours. However, the Early Warning Score had been calculated incorrectly, and no escalation had occurred.

What evidence is there that rapid response systems are effective in preventing patient deterioration and improving outcomes?

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Haemofiltration in Sepsis

Haemofiltration in Sepsis

A young IV drug user was admitted with septic shock secondary to staphylococcal sepsis with bilateral shadowing on CXR. He rapidly required intubation due to hypoxia, and institution of vasopressor support. He had a significant metabolic acidosis and consequently was commenced on haemofiltration. Transthoracic echocardiography revealed a large tricuspid vegetation. After 48 hours of haemofiltration, his acidosis haf normalised, and pressor requirements had reduced. He had a prolonged respiratory wean before being transferred to a cardiothoracic centre.

What is the role of haemofiltration (or other modes of renal replacement therapy) in severe sepsis and septic shock?
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Lactate Physiology and Predicting Disease Severity

Lactate Physiology and Predicting Disease Severity

A middle aged man presented with urosepsis after several days antibiotic therapy in the community. He was in septic shock, with tachypnoea, tachycardia and hypotension. He had raised inflammatory markers and acute kidney injury. His initial lactate level was 14mmol/L with a significant metabolic acidosis (base deficit 21). He was commenced on iv antibiotics, noradrenaline and renal replacement therapy. Lactate levels cleared to less than 2mmol/L over the next 24hrs. He weaned off noradrenaline in 72 hours and CVVHDF over the next 5 days.

How is lactate produced and what is its significance in predicting the severity of critical illness?

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Medical Management of Abdominal Compartment Syndrome

Medical Management of Abdominal Compartment Syndrome

An elderly man was admitted after a Hartman’s procedure with primary closure for a perforated sigmoid diverticulum with four quadrant peritonitis. Postoperatively, he remained ventilated and noradrenaline dependent. His intra-abdominal pressures gradually rose from 15 to 24mmHg. Urine output was poor, and he required peak pressures of 28cmH2O to achieve 6ml/kg tidal volumes. Vasopressor requirements gradually increased and a diagnosis of abdominal compartment syndrome was made. Medical management was attempted with fluid resuscitation, increased sedation, aspiration of nasogastric tube and neuromuscular blockade. However this did not improve the intra-abdominal pressures so the patient returned to theatre laparostomy and VAC dressing. On return from theatre, intra-abdominal pressures stabilised between 12 and 15mmHg. Noradrenaline requirements fell and urine output improved. The abdomen was closed on day 5 and he was discharged from ICU on day 10.

What non-surgical strategies can be used to reduce intra-abdominal pressure?

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