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

 

Advance Decisions in Critical Care

 

An 85 year old man with good pre-morbid function was admitted to the ICU following emergency laparotomy for a ischaemic perforation of small bowel. He had undergone a small bowel resection and primary anastomosis. Preoperatively, the patient had been delirious and unable to consent for surgery, assent was granted by his wife.

Postoperatively, the patient required mechanical ventilation, vasopressor support and renal replacement on admission. He stabilised by day 5, but remained mechanically ventilated. On day 5 of admission, during a discussion between the surgeon and the patient’s wife, the wife admitted regret that she had not had “better” discussions with the surgeons pre-operatively and raised doubts as to whether the patient would have wanted such treatment. Following those discussions between the wife and surgical team, limitations on care were placed; renal replacement therapies would not be restarted and vasopressor support would not be escalated beyond the existing level. A DNR order was implemented. On day 10, during discussion with the duty ICU consultant, it emerged that the patient had a written advance decision refusing “aggressive medical treatment”.

 

The patient continued to improve but could not be weaned from ventilation. A percutaneous tracheostomy was sited on day 10. On day 15 he was liberated from mechanical ventilation and able to use a speaking valve. He had regained mental capacity sufficient to discuss his care and wished to continue given the progress he had made. It was agreed that he would not be mechanically ventilated in the event of deterioration and the existing DNR order was confirmed. Subsequently, it became apparent that the small bowel anastomosis was leaking; it was agreed that treatment would be non-operative.

In total the patient was treated on ICU for 20 days before he was placed on an end of life pathway and died.

 

What are the implications of Advance Decisions on Intensive Care?Read More »

Alpha-2 agonists for sedation

 

A 66 year old woman was admitted to the ICU with acute type II respiratory failure secondary to a community acquired pneumonia (CURB-65 score 4) complicating severe COPD (FEV1 40% predicted). Collateral history revealed many concerning features; the patient had a poor exercise tolerance (mMRC dyspnoea scale score 3, exercise tolerance <100m), was alcohol dependent (drinking 120 units per week) and previously had been admitted to hospital with an exacerbation of COPD requiring NIV, and treatment for acute alcohol withdrawal.

 

Mechanical ventilation was commenced using a lung-protective strategy with permissive hypercapnia. Sedation was achieved using remifentanil and propofol, targeting a Richmond Agitation Scale Score (RASS) of -2 to 0. A noradrenaline infusion was commenced to maintain a mean arterial pressure of ≥65mmHg. A neutral cumulative fluid balance was targeted. Broad-spectrum antimicrobial therapy was continued as per local antimicrobial guidelines. Intravenous B vitamins were administered and enteral feeding was established via a nasogastric tube.

In view of the patient’s comparatively poor pre-morbid function and high risk of delirium, early extubation to NIV was identified as the preferred strategy. By day 3 the patient had improved such that this became a realistic goal. In order to prevent acute alcohol withdrawal, yet use benzodiazepines sparingly to avoid associated respiratory depression, remifentanil-propofol sedation was substituted for a clonidine infusion, which was continued following extubation. Low doses of chlordiazepoxide were used as rescue therapy in accordance with Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-Ar) scoring.

The patient progressed well, was weaned from both NIV and clonidine and was discharged from HDU to a respiratory ward on day 8. She survived to hospital discharge.

 

What role do Alpha-2 Agonists have for sedation in critical care?Read More »

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 »

Invasive Fungal Infections on ICU

A 42 year old woman was admitted to the intensive care unit with necrotising pancreatitis. She required sedation and mechanical, vasopressors to maintain adequate mean arterial pressure and extensive crystalloid resuscitation. Enteral nutrition was initially maintained via nasogastric feeding. She was treated with empirical broad-spectrum antibiotics (meropenem) and was prescribed antifungal prophylaxis (fluconazole) at the request of the hepatobiliary surgical team.

 

The patient experienced a prolonged systemic inflammatory response syndrome. She ultimately underwent a pancreatic necrosectomy and required recurrent radiologically-guided percutaneous drainage of intra-abdominal collections. For a large proportion of her ICU admission, enteral nutrition failed and the patient required total parenteral nutrition. Candida albicans was isolated from central venous catheter exits sites, drain exit sites, drain fluid, urine and sputum on several occasions, but there was never any evidence of invasive fungal disease.

The patient was eventually discharged from ICU and survived to discharge from hospital. She was left dependent on pancreatic enzyme replacement and subcutaneous insulin therapy.

Describe the incidence, clinical features and management of fungal infections in non-neutropaenic, non-transplant critical care patients.Read More »