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Three Part Question

For [Adult (16-65 year old) patients presenting to Emergency Departments with signs of sepsis and ascites] does [early paracentesis vs. late paracentesis and paracentesis and blood cultures vs. blood cultures alone] lead to [an improved bacterial yield and an increased pick up of pathogens therefore more targeted antibiotic use and or a change in antibiotics within 24 to 48 hours; therefore a reduced length of stay and reduced morbidity and mortality]

Clinical Scenario

A 37 year old man presents to the emergency department with a cough and feeling generally unwell. He has signs of sepsis with a high; temperature, pulse, lactate and respiratory rate. He is assessed in triage and taken to the resuscitation room. He has a history of alcohol excess and known cirrhosis of the liver.

He has some diffuse crackles at his left base but no clinical changes on his chest x-ray. He has a soft but distended abdomen, with known ascites, which he feels has increased in the last 48 hours. He is treated for sepsis of unknown origin and transferred to the acute medical assessment area. Within 24 hours he has deteriorated, he is not accepted for intensive care due to his high child-Pugh score and after 12 hours of fluids and antibiotics he has a cardiac arrest and dies. The post-mortem report concludes spontaneous bacterium peritonitis as the cause of death.

Search Strategy

Search Strategy
Ovid Medline form 1946- 1st week of December

Exp Paracentesis/ OR exp Ascites/ OR exp Liver failure/ OR Spontaneous Bacterial peritonitis AND exp Sepsis

Exp Paracentesis/ OR exp Ascites/ OR exp Liver failure AND Exp Emergency department$/ OR exp Emergency service$
Limited to English Language and Humans

3 papers found

Cochrane database: no further papers

Google scholar 1 further paper

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Chinmaya Kumar Bal 2017 India	170 culture negative neutrocytic ascites patients With decompensated cirrhosis with the first episode of ascites were included in the study.	Cohort Study	50 day mortality rate 39.41% for culture negative neutrocytic ascites Mean time to death 14 days Compared to 43.1% for SBP- results from a different paper	Hazard ratios mortality: AKI 2.21 (1.33-3.66) p=0.002 Sepsis 1.89 (1.08-3.32) p=0.026 Raised INR 1.20 (1.01-1.44) p=0.036 Hepatic encephalopathy and Child Pugh score are poor predictive values for mortality	No power calculation done for a primary outcome Many outcomes discussed and statistical analysis done on these outcomes
John Kim 2014 America	Adults with clinical evidence of cirrhosis and spontaneous bacterial peritonitis 239 patients were included in the study	prospective cohort	Primary outcome was in-hospital mortality Secondary outcomes included acute kidney injury, intensive care days, hospital days, 3-month mortality, and 1-year overall survival. Patients who had a DP had a higher mortality	Early paracentesis (EP) was defined as within 12 hours of admission and delayed paracentesis (DP) 12-72 hours. Mortality in DP = 27% Mortality in EP = 13% In EP group time to paracentesis and mortality: < 6 hours 10 % 6-11 hours 20% 12-23 hours 23% 24-48 hours 24% >48 hours 38% When expressed as a continuous variable there is a 3.3% (95% CI= 1.3-5.4%) increase in mortality with every hour delay in paracentesis 34% of patients had an organism isolated of these patients: 40% blood culture BC alone 37% in ascitic fluid AF alone 22% in both BC and AF	Patients who had a DP also had a delayed administration of antibiotics of any type. No data is presented for the timing of the first dose of antibiotic given this information would allow a comparison if the dose of antibiotic vs. specific antibiotics for a known pathogen. There is also no comment as to whether the antibiotic has been changed due to the culture result. Not all patients received IV albumin which has been shown to increase survival in cirrhotic patients.
John Gaetano 2015 America	Adult patients non-electively admitted with a discharge diagnosis of Cirrhosis and ascites as recorded on the American Nationwide Inpatient Sample in 2011. 31,614 patients were included.	Retrospective cohort	Primary outcome measures were in-hospital mortality, length of stay and total hospitalisation cost. With paracentesis measured as an independent variable. In-hospital mortality =7.6% Mean Length of stay = 7.28 days Mean Hospitalisation cost $61,658.	51% underwent paracentesis during their admission. Admission at a weekend was associated with reduced paracentesis rates 49% vs. 52 % (p=0.001) Paracentesis occurred more frequently in patients with Leukocytosis 58%, acidosis 53% and AKI 56% (p<0.001). Compared to patients with Abdominal pain 45% and fever 40%. (p<0.001). Overall hospital mortality was 7.6 % with increased mortality in those who did not undergo paracentesis 8.9% vs. 6.3% p<0.001 Among those diagnosed with SBP those who received early paracentesis the Length of stay was reduced to 7.55 vs. 11.45 days p<0.001)	No data presented on the use of antibiotics and the results of paracentesis guiding the patients care. They conclude that their paper shows that by not doing paracentesis a subset of patients are left with undiagnosed SBP and this is the cause of increased mortality in this group. However they have come to this conclusion without studying the treatment that the patients received and comparing the 2 groups. IT may be that doctors treating the group who had paracentesis are doctors who are more likely to prescribe albumin and antibiotics.
Eeric Orman 2014 America	Adult patients with a discharge code of Ascites, Spontaneous bacterial peritonitis or hepatic encephalopathy with a secondary diagnosis of ascites. With all patients having a secondary diagnosis of cirrhosis. 17,711 met the inclusion criteria and 10,743 had a paracentesis performed.	Retrospective Cohort	The authors sought to examine the performance of a paracentesis and early vs. delayed paracentesis (<1 day vs. >1 day) with the primary outcome as in-hospital mortality. They found that those who had a paracentesis had a reduced in hospital mortality but a longer hospital stay and higher cost.	Patients who underwent paracentesis had lower in-hospital mortality than those who did not 6.5% vs. 8.5% P=0.03 Mortality was higher in those with: Sepsis 27.2% AKI 16.4% The mortality benefit in paracentesis was seen for those with a diagnosis of encephalopathy or ascites and not for those with a diagnosis of SBP. Those who were admitted to non-teaching hospitals and over the weekend were more likely to have a delayed paracentesis Mean length of stay for those who underwent paracentesis was 6.6 vs. 5.3 for those who did not	No treatments were presented so again we are unable to comment as to the benefit of paracentesis vs that of antibiotics

Comment(s)

Patients with cirrhosis are predisposed to infection for many reasons, with the infection rate in these patients believed to be as high as 30% of hospitalised patients with cirrhosis. The reasons behind this are multifactorial; • They have impaired immunity, • An overgrowth of bacteria within the gut • An increased passage of bacteria from the gut known as bacterial translocation (BT) Once the patient has an infection it can easily lead to systemic inflammatory response syndrome (SIRS) and sepsis in a patient already predisposed to hypotension, renal dysfunction, coagulation disorders and encephalopathy. The most common infections seen in cirrhotic patients are SBP, 25%, Urinary tract infection 20%, pneumonia 15% and bacteraemia, 12%.5,6 The diagnosis of SBP is difficult as the clinical presentation can range from abdominal pain, fever and GI symptoms, to end organ failure, to no specific symptoms at all. Due to recent drives to promote the treatment of sepsis and the introduction of a sepsis bundle into many hospitals deaths from sepsis are decreasing but the death rate for those with ascites due to cirrhosis is still high, at around 20%. The surviving sepsis campaign has so successfully promoted its steps it is now almost a knee jerk reaction to give early antibiotics and take blood cultures to anyone with a high temperature. However we still do not perform a paracentesis on admission despite this group of patients having some of the highest levels of mortality when combined with sepsis. All the papers above except Orman et al. agree that an early paracentesis leads to reduced in-hospital mortality. Orman et al. only found a benefit for those with a diagnosis of ascites and encephalopathy but not that of SPB. There is no comment in the paper as to how a patient was diagnosed with SBP without conformation on paracentesis. Orman et al. did not show a statistical significance to having an early paracentesis compared to the other papers. Kim et al. stated that there was a 3.3% increase in mortality for every hour delay in paracentesis. Although all these figures and statics are impressive and lead you to believe that early paracentesis is a life saving procedure it must be considered that this procedure cannot be taken in isolation. None of the above papers have studied the use of antibiotics or albumin as a resuscitation fluid. Within these admissions it may be that the hospitals or doctors that performed paracentesis on admission were also those who prescribed broad spectrum antibiotics early and used albumin as a resuscitation fluid. Paracentesis may just go hand in hand with good clinical care. Kim et al. stated that 34% of patients had an organism isolated and of those 37% grew that organism in the ascitic fluid culture alone comparable to the 40% who grew an organism in blood cultures alone. Within the paper they do not state if that resulted in a change in antibiotics. I feel that this is a significant result; if these patients had not undergone a paracentesis 37% of those who grew an organism (13% of the whole patient group) would not have a result. In this current era of multi-drug resistant organisms this is a significant factor to consider. However this does not answer if they paracentesis lead to a change in antibiotics so part of the three part question is left unanswered. Gaetano et al. and Orman et al. have conflicting results on the length of stay for patients. Orman et al. stated that patients who underwent paracentesis had an increased length of stay compared to Gaetano et al. who found the opposite. Although the two authors are looking at slightly different subsets of patients it is difficult to decide whose result is valid. Orman et al. have published their work earlier so practice may have changed since then, it also may be that in this paper it is the high acuity patients who are having the paracentesis thus their length of stay is also affected by their need for more treatment. From this it is impossible to ascertain who is correct. Within these papers there is no discussion around complications of the paracentesis. Although paracentesis is a relatively safe procedure it is always pertinent to consider that these patients could have complications. The main complication to consider is that of haemorrhage, with an altered coagulopathy all invasive procedures must be done with caution.

Clinical Bottom Line

Early paracentesis in septic patients with ascites reduces mortality and increases bacterial yield only when combined with a bundle of care designed specifically for this unwell subset of septic patients.

References

1. Chinmaya Kumar Bal, Vikram Bhatia and Ripu Daman Predictors of fifty days in hospital mortality in patients with culture negative ascites GMC Gastroenterology (2017) 109;1436-1442
2. ohn Kim, Michelle Tsukamoto, Arvind Mathur, Yashar Ghomri, Linda Hou, Sarah Sheibani and Bruce Runyon, Delayed Paracentesis is associated with increased in-hospital mortality in patients with spontaneous bacterial peritonitis American Journal of gastroenterology 2014 109;1436-1442
3. 3) John Gaetano, Dejan Micic, Andrew Aronsohn, Gautham Reddy, Helen Te, Nancy Reau and Donald Jensen The benefit of paracentesis on hospitalised adults with cirrhosis and ascites journal of gastroenterology and hepatology (2016) 31;1025-1030
4. Eeric Orman, Paul Hayashi, Ramon Bataller and Sidney Barritt Paracentesis is associated with reduced mortality in patients hospitalised with cirrhosis and ascites Clincal gastroenterology and hepatology (2014) 12;496-503