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1.  Predictors of septic shock in obstructive acute pyelonephritis 
World Journal of Urology  2013;32(3):803-811.
Purpose
Acute pyelonephritis (APN) with obstructive uropathy is not uncommon and often causes serious conditions including sepsis and septic shock. We assessed the risk factors for septic shock in patients with obstructive APN associated with upper urinary tract calculi.
Methods
We retrospectively studied 69 patients with obstructive APN associated with upper urinary tract calculi who were admitted to our hospital. Emergency drainage for decompression of the renal collecting system was performed for empirical treatment in cases of failure of initial treatment and for severe cases. We assessed the risk factors for septic shock by multivariate logistic regression analysis.
Results
Overall, 45 patients (65.2 %) underwent emergency drainage and 23 (33.3 %) patients showed septic shock. Poor performance status and the presence of diabetes mellitus (DM) in the septic shock group were more common than in the non-septic shock group (p = 0.012 and p = 0.011, respectively). The platelet count and serum albumin level in the septic shock group were significantly lower than in the non-septic shock group (p = 0.002 and p = 0.003, respectively). Positive rates of midstream urine culture and blood culture in the septic shock group were significantly higher than in the non-septic shock group (p = 0.022 and p = 0.001, respectively). Multivariate analysis showed that decreases in the platelet count (OR 5.43, p = 0.014) and serum albumin level (OR 5.88, p = 0.023) were independent risk factors for septic shock.
Conclusion
Patients with obstructive APN associated with upper urinary tract calculi who have decreases in platelet count and serum albumin level should be treated with caution against the development of septic shock.
doi:10.1007/s00345-013-1166-4
PMCID: PMC4031390  PMID: 24037335
Acute pyelonephritis; Upper urinary tract calculi; Septic shock; Platelets; Albumin
2.  Clinical and epidemiological features and prognosis of complicated pyelonephritis: a prospective observational single hospital-based study 
BMC Infectious Diseases  2014;14(1):639.
Background
Complicated pyelonephritis (cPN), a common cause of hospital admission, is still a poorly-understood entity given the difficulty involved in its correct definition. The aim of this study was to analyze the main epidemiological, clinical, and microbiological characteristics of cPN and its prognosis in a large cohort of patients with cPN.
Methods
We conducted a prospective, observational study including 1325 consecutive patients older than 14 years diagnosed with cPN and admitted to a tertiary university hospital between 1997–2013. After analyzing the main demographic, clinical and microbiological data, covariates found to be associated with attributable mortality in univariate analysis were included in a multivariate logistic regression model.
Results
Of the 1325 patients, 689 (52%) were men and 636 (48%) women; median age 63 years, interquartile range [IQR] (46.5-73). Nine hundred and forty patients (70.9%) had functional or structural abnormalities in the urinary tract, 215 (16.2%) were immunocompromised, 152 (11.5%) had undergone a previous urinary tract instrumentation, and 196 (14.8%) had a long-term bladder catheter, nephrostomy tube or ureteral catheter. Urine culture was positive in 813 (67.7%) of the 1251 patients in whom it was done, and in the 1032 patients who had a blood culture, 366 (34%) had bacteraemia. Escherichia coli was the causative agent in 615 episodes (67%), Klebsiella spp in 73 (7.9%) and Proteus ssp in 61 (6.6%). Fourteen point one percent of GNB isolates were ESBL producers. In total, 343 patients (25.9%) developed severe sepsis and 165 (12.5%) septic shock. Crude mortality was 6.5% and attributable mortality was 4.1%. Multivariate analysis showed that an age >75 years (OR 2.77; 95% CI, 1.35-5.68), immunosuppression (OR 3.14; 95% CI, 1.47-6.70), and septic shock (OR 58.49; 95% CI, 26.6-128.5) were independently associated with attributable mortality.
Conclusions
cPN generates a high morbidity and mortality and likely a great consumption of healthcare resources. This study highlights the factors directly associated with mortality, though further studies are needed in the near future aimed at identifying subgroups of low-risk patients susceptible to outpatient management.
doi:10.1186/s12879-014-0639-4
PMCID: PMC4267459  PMID: 25492862
Urinary tract infection; Complicated; Epidemiology; Prognosis
3.  Severe Maternal Sepsis in the UK, 2011–2012: A National Case-Control Study 
PLoS Medicine  2014;11(7):e1001672.
Marion Knight and colleagues conducted a national prospective case-control study in the UK from June 2011 through May 2012 to estimate the incidence, describe the causative organisms and sources of infection, and identify the risk factors for severe maternal sepsis.
Please see later in the article for the Editors' Summary
Background
In light of increasing rates and severity of sepsis worldwide, this study aimed to estimate the incidence of, and describe the causative organisms, sources of infection, and risk factors for, severe maternal sepsis in the UK.
Methods and Findings
A prospective case-control study included 365 confirmed cases of severe maternal sepsis and 757 controls from all UK obstetrician-led maternity units from June 1, 2011, to May 31, 2012. Incidence of severe sepsis was 4.7 (95% CI 4.2–5.2) per 10,000 maternities; 71 (19.5%) women developed septic shock; and five (1.4%) women died. Genital tract infection (31.0%) and the organism Escherichia coli (21.1%) were most common. Women had significantly increased adjusted odds ratios (aORs) of severe sepsis if they were black or other ethnic minority (aOR = 1.82; 95% CI 1.82–2.51), were primiparous (aOR = 1.60; 95% CI 1.17–2.20), had a pre-existing medical problem (aOR = 1.40; 95% CI 1.01–1.94), had febrile illness or were taking antibiotics in the 2 wk prior to presentation (aOR = 12.07; 95% CI 8.11–17.97), or had an operative vaginal delivery (aOR = 2.49; 95% CI 1.32–4.70), pre-labour cesarean (aOR = 3.83; 95% CI 2.24–6.56), or cesarean after labour onset (aOR = 8.06; 95% CI 4.65–13.97). Median time between delivery and sepsis was 3 d (interquartile range = 1–7 d). Multiple pregnancy (aOR = 5.75; 95% CI 1.54–21.45) and infection with group A streptococcus (aOR = 4.84; 2.17–10.78) were associated with progression to septic shock; for 16 (50%) women with a group A streptococcal infection there was <2 h—and for 24 (75%) women, <9 h—between the first sign of systemic inflammatory response syndrome and a diagnosis of severe sepsis. A limitation of this study was the proportion of women with sepsis without an identified organism or infection source (16.4%).
Conclusions
For each maternal sepsis death, approximately 50 women have life-threatening morbidity from sepsis. Follow-up to ensure infection is eradicated is important. The rapid progression to severe sepsis highlights the importance of following the international Surviving Sepsis Campaign guideline of early administration of high-dose intravenous antibiotics within 1 h of admission to hospital for anyone with suspected sepsis. Signs of severe sepsis in peripartum women, particularly with confirmed or suspected group A streptococcal infection, should be regarded as an obstetric emergency.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, nearly 300,000 women worldwide die during pregnancy or labour, or shortly after. According to a recent World Health Organization estimate, sepsis (blood poisoning) is responsible for 10.7% of these maternal deaths. Sepsis is caused by an inappropriate immune response to an infection. Normally, when bacteria or other microbes enter the human body, the immune system efficiently destroys the invaders. In sepsis, the immune system goes into overdrive, and the chemicals it releases into the blood to combat infection trigger widespread inflammation. This inflammation leads to the formation of small blood clots and leaky blood vessels that block the flow of blood to the vital organs. In the most severe cases (septic shock), blood pressure falls to dangerously low levels, multiple organs fail, and the patient can die. Symptoms of sepsis include fever, rapid breathing, and a fast heart rate. Sepsis, which often progresses rapidly, can be treated in its early stages with antibiotics alone. People with severe sepsis need to be admitted to an intensive care unit, where their vital organs can be supported while the infection is treated.
Why Was This Study Done?
Deaths from maternal sepsis mainly occur in low- and middle-income countries, but the rate of such deaths is increasing in countries with advanced healthcare systems. In the UK, for example, the incidence (the number of cases) of fatal maternal sepsis has increased markedly over the past two decades, and although the absolute risk of maternal death from sepsis is low, increasing numbers of women are experiencing severe maternal sepsis. To avoid preventable maternal illness and death in the UK, it is essential that clinical management and infection control strategies for maternal sepsis are improved. Here, to learn more about the incidence of maternal sepsis, the causative organisms and sources of infection, and the risk factors for maternal sepsis in the UK, the researchers undertake a national case-control study of severe maternal sepsis. A case-control study compares the characteristics of individuals with and without a given disease.
What Did the Researchers Do and Find?
For this study, clinicians in all the UK obstetrician-led maternity units (obstetricians care for women throughout pregnancy, labour, and the post-labour period) sent information about every woman who developed severe sepsis between June 2011 and May 2012 (365 cases) and about two unaffected (control) women per case to the United Kingdom Obstetric Surveillance System (UKOSS). Using this information and data on the number of maternities in the UK during this 12-month period, the researchers calculated that the incidence of severe sepsis was 4.7 per 10,000 maternities. Seventy-one women with severe sepsis (19.5% of cases) developed septic shock, and five women (1.4% of cases) died. The most common source of sepsis (implicated in about a third of cases) was a genital tract infection. Statistical analyses identified several risk factors for severe maternal sepsis, including having a fever or taking antibiotics in the two weeks preceding sepsis and all types of operative delivery (including cesarean delivery). Importantly, although Escherichia coli was the most common causative organism in severe maternal sepsis (present in a fifth of cases), infection with group A streptococcus was strongly associated with progression to septic shock. Moreover, in half the women with a group A streptococcal infection, severe sepsis was diagnosed within two hours of the first signs of a systemic inflammatory response.
What Do These Findings Mean?
These findings show that for every death from maternal sepsis in the UK, about 50 women develop life-threatening severe sepsis, that the onset of severe sepsis is very rapid, and that women who have recently had an infection are at particularly high risk of developing maternal sepsis. Although some pregnant women who developed severe sepsis during the study period may not have been included in the study, these findings have important clinical implications for the management of maternal sepsis in the UK and elsewhere. The findings suggest that pregnant or recently pregnant women with an infection need closer attention than women who are not pregnant, and adequate follow-up to ensure eradication of the infection. The findings also highlight the importance of giving high-dose intravenous antibiotics to anyone with suspected sepsis within an hour of admission to hospital as recommended by the international Surviving Sepsis Campaign, an initiative that was developed to improve the management, diagnosis, and treatment of sepsis. Finally, these findings suggest that signs of severe sepsis, particularly in women with a confirmed or suspected group A streptococcal infection, should be regarded as an obstetric emergency.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001672.
The UK National Health Service Choices website has information about sepsis
The international Surviving Sepsis Campaign guidelines for the treatment of sepsis are available through the campaign's website
The Sepsis Alliance, a US not-for-profit organization, also provides information about sepsis for patients and their families (in English and Spanish), including information about maternal sepsis and several personal stories about maternal sepsis (see the stories of Alanna Basinger, Alisa Proctor, Sandy C, and Natalie Banathy)
The not-for profit UK Sepsis Trust is another useful source of information about sepsis that includes patient stories
MedlinePlus provides links to additional resources about sepsis (in English and Spanish)
UKOSS provides more information about its national case-control study on severe maternal sepsis in the UK
doi:10.1371/journal.pmed.1001672
PMCID: PMC4086731  PMID: 25003759
4.  The Innate Immune Response in HIV/AIDS Septic Shock Patients: A Comparative Study 
PLoS ONE  2013;8(7):e68730.
Introduction
In recent years, the incidence of sepsis has increased in critically ill HIV/AIDS patients, and the presence of severe sepsis emerged as a major determinant of outcomes in this population. The inflammatory response and deregulated cytokine production play key roles in the pathophysiology of sepsis; however, these mechanisms have not been fully characterized in HIV/AIDS septic patients.
Methods
We conducted a prospective cohort study that included HIV/AIDS and non-HIV patients with septic shock. We measured clinical parameters and biomarkers (C-reactive protein and cytokine levels) on the first day of septic shock and compared these parameters between HIV/AIDS and non-HIV patients.
Results
We included 30 HIV/AIDS septic shock patients and 30 non-HIV septic shock patients. The HIV/AIDS patients presented low CD4 cell counts (72 [7-268] cells/mm3), and 17 (57%) patients were on HAART before hospital admission. Both groups were similar according to the acute severity scores and hospital mortality. The IL-6, IL-10 and G-CSF levels were associated with hospital mortality in the HIV/AIDS septic group; however, the CRP levels and the surrogates of innate immune activation (cytokines) were similar among HIV/AIDS and non-HIV septic patients. Age (odds ratio 1.05, CI 95% 1.02-1.09, p=0.002) and the IL-6 levels (odds ratio 1.00, CI 95% 1.00-1.01, p=0.05) were independent risk factors for hospital mortality.
Conclusions
IL-6, IL-10 and G-CSF are biomarkers that can be used to predict prognosis and outcomes in HIV/AIDS septic patients. Although HIV/AIDS patients are immunocompromised, an innate immune response can be activated in these patients, which is similar to that in the non-HIV septic population. In addition, age and the IL-6 levels are independent risk factors for hospital mortality irrespective of HIV/AIDS disease.
doi:10.1371/journal.pone.0068730
PMCID: PMC3708901  PMID: 23874739
5.  Acute Kidney Injury in Patients with Sepsis and Septic Shock: Risk Factors and Clinical Outcomes 
Yonsei Medical Journal  2013;54(4):965-972.
Purpose
The aim of this study was to investigate clinical characteristics and risk factors of acute kidney injury (AKI) in patients with sepsis and septic shock. Additionally, we explored whether the severity of AKI affects on the clinical outcomes.
Materials and Methods
Data were collected retrospectively in a single center. Among 5680 patients who visited emergency department from January to December 2010, 992 patients with sepsis and septic shock were enrolled. Patients were divided into two groups, patients who developed AKI or not, to compare the baseline characteristics, and laboratory and physiologic data. Patients with AKI were subdivided according to its stages for survival analysis.
Results
AKI was developed in 57.7% of patients. Multivariable logistic regression analysis revealed that development of septic AKI was associated with older age, pre-existing chronic kidney disease, use of angiotensin converting enzyme inhibitor or angiotensin receptor blocker, presence of shock, positive blood culture results, and low white blood cell and platelet counts. Hospital mortality was higher in AKI group. Crude Kaplan-Meier survival curves demonstrated reduced 30-day survival rate was significantly associated with the severity of acute kidney injury.
Conclusion
The development of septic AKI was associated with poor clinical outcomes. Furthermore, the severity of AKI was associated with increased mortality.
doi:10.3349/ymj.2013.54.4.965
PMCID: PMC3663224  PMID: 23709433
Acute kidney injury; mortality; risk factors; sepsis; septic shock
6.  Pyelonephritis (acute) in non-pregnant women 
Clinical Evidence  2011;2011:0807.
Introduction
Pyelonephritis is usually caused by ascent of bacteria, most often Escherichia coli, from the bladder, and is more likely in people with structural or functional urinary tract abnormalities. The prognosis is good if pyelonephritis is treated appropriately, but complications include renal abscess, renal impairment, and septic shock.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of: antibiotic treatments for acute pyelonephritis in women with uncomplicated infection; inpatient versus outpatient management in women with uncomplicated infection; and analgesia in uncomplicated acute pyelonephritis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found three systematic reviews, RCTs, or observational studies that met our inclusion criteria.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics (intravenous), antibiotics (oral), antibiotics (switch therapy), inpatient versus outpatient management, non-steroidal anti-inflammatory drugs, simple analgesics (non-opioid), and urinary analgesics.
Key Points
Pyelonephritis is usually caused by ascent of bacteria from the bladder, most often Escherichia coli, and is more likely in people with structural or functional urinary tract abnormalities. The prognosis of acute uncomplicated pyelonephritis is good if pyelonephritis is treated appropriately, but complications include renal abscess, renal impairment, and septic shock.
We found no direct information about whether oral or intravenous antibiotics are better than no active treatment. However, consensus holds that these drugs are effective. We don't know how any one oral antibiotic regimen compares with another, or what the optimum duration of treatment is, although it may be sensible to continue treatment for at least 10 days. Broader spectrum antibiotics, such as quinolones, may be more effective compared with narrower spectrum antibiotics, such as ampicillin, amoxicillin, or trimethoprim–sulfamethoxazole (co-trimoxazole), in areas where resistance to these agents is common.We don't know whether any particular switch regimen (intravenous antibiotics followed by oral antibiotics) is better than another, or how switch antibiotic regimens compare with oral antibiotic regimens. We found no information from RCTs on the time to change from intravenous to oral antibiotics.We don't know which is the most effective intravenous antibiotic regimen, or the optimum duration of treatment.
We found no RCTs comparing inpatient with outpatient treatment. Clinical judgement of the severity of infection and the quality of ambulatory care should be considered in the decision to admit a patient into hospital.
We found no RCTs assessing the effects of simple analgesics, NSAIDs, or urinary analgesics on pain from uncomplicated pyelonephritis. NSAIDs may worsen renal function and should be used with caution in women with pyelonephritis.
PMCID: PMC3217727  PMID: 21477395
7.  A rare association of emphysematous pyelonephritis with unrecognized diabetes and polycystic kidney 
Indian Journal of Nephrology  2009;19(1):20-22.
Emphysematous pyelonephritis (EPN) is a rare, severe, gas-forming infection for which the treatment of choice is often an immediate nephrectomy, although many reports exist of conservative treatment of cases with antibiotic therapy and percutaneous drainage of abscesses. It usually occurs in diabetic patients and less frequently in subjects with an obstruction of the corresponding renoureteral unit; other predisposing factors are not common. We report here the case of a 51 year-old woman with a rare association of unrecognized diabetes and bilateral polycystic kidney disease who developed monolateral EPN. She had an emergency right nephrectomy and was admitted to Intensive Care Unit (ICU) for septic shock after surgery, requiring intensive resuscitation. The patient was managed with Coupled Plasma Filtration Adsorption (CPFA). Her clinical conditions rapidly improved and the hemofiltration was soon suspended. Urine and blood cultures were positive for the same Escherichia coli, which was susceptible to all tested antibiotics. The patient was transferred to the Nephrology Division and was discharged from the hospital without further dialysis after 34 days. This case report is somewhat unique because of the unusual association between undetected diabetes and polycystic kidney as predisposing factors of a severe infection of the urinary tract.
doi:10.4103/0971-4065.50676
PMCID: PMC2845189  PMID: 20352007
Emphysematous pyelonephritis (EPN); diabetes mellitus; polycystic kidney; dialysis
8.  Emphysematous Cystitis: Report of an Atypical Case 
Case Reports in Urology  2011;2011:280426.
We report the atypical case of a nondiabetic 66-year old male with severe abdominal pain and vomiting who was found to have emphysematous cystitis. Of all gas-forming infections of the urinary tract emphysematous cystitis is the most common and the least severe. The major risk factors are diabetes mellitus and urinary tract obstruction. Most frequent causative pathogens are Escherichia coli and Klebsiella pneumoniae. The clinical presentation is nonspecific and ranges from asymptomatic urinary tract infection to urosepsis and septic shock. The diagnosis is made by abdominal imaging. Treatment consists of broad-spectrum antibiotics, bladder drainage, and management of the risk factors. Surgery is reserved for severe cases. Overall mortality rate of emphysematous cystitis is 7%. Immediate diagnosis and treatment is necessary because of the rapid progression to bladder necrosis, emphysematous pyelonephritis, urosepsis, and possibly fatal evolution.
doi:10.1155/2011/280426
PMCID: PMC3350004  PMID: 22606608
9.  Factors associated with septic shock and mortality in generalized peritonitis: comparison between community-acquired and postoperative peritonitis 
Critical Care  2009;13(3):R99.
Introduction
The risk factors associated with poor outcome in generalized peritonitis are still debated. Our aim was to analyze clinical and bacteriological factors associated with the occurrence of shock and mortality in patients with secondary generalized peritonitis.
Methods
This was a prospective observational study involving 180 consecutive patients with secondary generalized peritonitis (community-acquired and postoperative) at a single center. We recorded peri-operative occurrence of septic shock and 30-day survival rate and analyzed their associations with patients characteristics (age, gender, SAPS II, liver cirrhosis, cancer, origin of peritonitis), and microbiological/mycological data (peritoneal fluid, blood cultures).
Results
Frequency of septic shock was 41% and overall mortality rate was 19% in our cohort. Patients with septic shock had a mortality rate of 35%, versus 8% for patients without shock. Septic shock occurrence and mortality rate were not different between community-acquired and postoperative peritonitis. Age over 65, two or more microorganisms, or anaerobes in peritoneal fluid culture were independent risk factors of shock. In the subgroup of peritonitis with septic shock, biliary origin was independently associated with increased mortality. In addition, intraperitoneal yeasts and Enterococci were associated with septic shock in community-acquired peritonitis. Yeasts in the peritoneal fluid of postoperative peritonitis were also an independent risk factor of death in patients with septic shock.
Conclusions
Unlike previous studies, we observed no difference in incidence of shock and prognosis between community-acquired and postoperative peritonitis. Our findings support the deleterious role of Enterococcus species and yeasts in peritoneal fluid, reinforcing the need for prospective trials evaluating systematic treatment against these microorganisms in patients with secondary peritonitis.
doi:10.1186/cc7931
PMCID: PMC2717471  PMID: 19552799
10.  Diagnostic value and prognostic evaluation of Presepsin for sepsis in an emergency department 
Critical Care  2013;17(5):R244.
Introduction
Presepsin levels are known to be increased in sepsis. The aim of this study was to evaluate the early diagnostic and prognostic value of Presepsin compared with procalcitonin (PCT), Mortality in Emergency Department Sepsis (MEDS) score and Acute Physiology and Chronic Health Evaluation II (APACHE II) score in septic patients in an emergency department (ED) and to investigate Presepsin as a new biomarker of sepsis.
Methods
This study enrolled 859 consecutive patients with at least two diagnostic criteria for systemic inflammatory response syndrome (SIRS) who were admitted to Beijing Chao-yang Hospital ED from December 2011 to October 2012, and 100 age-matched healthy controls. Patients were stratified into four groups: SIRS, sepsis, severe sepsis, and septic shock. Plasma Presepsin and serum PCT were measured, and MEDS score and APACHE II score were calculated at enrollment. Comparisons were analyzed using the Kruskal-Wallis and Mann–Whitney U tests.
Results
On admission, the median levels of plasma Presepsin increased with sepsis severity. The areas under the receiver operating characteristic (AUC) curves of Presepsin were greater than those of PCT in diagnosing sepsis, and predicting severe sepsis and septic shock. The AUC of Presepsin for predicting 28-day mortality in septic patients was slightly lower than that of PCT, MEDS score and APACHE II score. The AUC of a combination of Presepsin and MEDS score or APACHE II score was significantly higher than that of MEDS score or APACHE II score alone in predicting severe sepsis, and was markedly higher than that of Presepsin alone in predicting septic shock and 28-day mortality in septic patients, respectively. Plasma Presepsin levels in septic patients were significantly higher in non-survivors than in survivors at 28 days’ follow-up. Presepsin, MEDS score and APACHE II score were found to be independent predictors of severe sepsis, septic shock and 28-day mortality in septic patients. The levels of plasma Presepsin were positively correlated with PCT, MEDS score and APACHE II score in every septic group.
Conclusion
Presepsin is a valuable biomarker for early diagnosis of sepsis, risk stratification, and evaluation of prognosis in septic patients in the ED.
doi:10.1186/cc13070
PMCID: PMC4056322  PMID: 24138799
11.  Emphysematous pyelonephritis in type II diabetes: A case report of an undiagnosed ureteric colic 
Cases Journal  2008;1:192.
Introduction
Emphysematous pyelonephritis (EPN) is a severe acute necrotising infection of the renal parenchyma and perirenal tissue, characterised by gas formation. 90% of cases are seen in association with diabetes mellitus. We report a case of undiagnosed ureteric obstruction in a type II diabetic, leading to EPN requiring emergency nephrectomy.
Case presentation
A 59-year-old type II tablet controlled diabetic woman presented complaining of a five day history of right sided abdominal pain associated with vomiting, abdominal distension and absolute constipation. There were no lower urinary tract symptoms. Past surgical history included an open appendectomy and an abdominal hysterectomy. On examination, she was haemodynamically stable, the abdomen was soft, distended, and tender in the right upper and lower quadrants with no bowel sounds. Investigations revealed a CRP of 365 and 2+ blood and nitrite positive on the urine dipstick. The AXR was reported as normal on admission, however when reviewed in retrospect revealed the diagnosis. She was managed, therefore, as having adhesional bowel obstruction and a simple UTI. After four days, a CT was organised as she was not settling. This showed a right pyohydronephrosis with gas in the collecting system secondary to an 8 mm obstructing ureteric calculus. The kidney was drained percutaneously via a nephrostomy and the patient was commenced on a broad spectrum intravenous antibiotics. Despite this, she went on to need an emergency nephrectomy for uncontrolled severe sepsis. She was discharged in good health 15 days later.
Conclusion
EPN carries a mortality of up to 40% with medical management alone. Early recognition of EPN in an obstructed kidney is essential to guide aggressive management, and in the presence of continued severe sepsis or organ dysfunction an urgent nephrectomy should be carried out. Diabetic patients who are known to have renal or ureteric calculi, whether symptomatic or not, should be considered for percutanous or ureteroscopic treatment. In the acute abdomen, the plain abdominal radiograph should always be viewed with respect to general surgical, vascular and urological differential diagnoses.
doi:10.1186/1757-1626-1-192
PMCID: PMC2565667  PMID: 18826627
12.  Long-term nephrostomy in an adult male spinal cord injury patient who had normal upper urinary tracts but developed bilateral hydronephrosis following penile sheath drainage: pyeloplasty and balloon dilatation of ureteropelvic junction proved futile: a case report 
Cases Journal  2009;2:9335.
Introduction
The consequences of spinal cord injury upon urinary bladder are readily recognised by patients and health care professionals, since neuropathic bladder manifests itself as urinary incontinence, or retention of urine. But health care professionals and persons with spinal cord injury may not be conversant with neuropathic dysmotility affecting the ureter and renal pelvis. We report an adult male patient with spinal cord injury, who developed bilateral hydronephrosis after he started managing neuropathic bladder by penile sheath drainage.
Case presentation
A male patient, born in 1971, sustained spinal cord injury following a motorbike accident in September 1988. In November 1988, intravenous urography showed normal upper tracts. He was advised spontaneous voiding with 2-3 catheterisations a day. In February 1995, this patient developed fever, chills and vomiting. Blood urea: 23.7 mmol/L; creatinine: 334 umol/L. Ultrasound revealed marked hydronephrosis of right kidney and mild hydronephrosis of left kidney. Bilateral nephrostomy was performed in March 1995. Right pyeloplasty was performed in May 1998. In July 2005, this patient developed urine infection and was admitted to a local hospital with fever and rigors. He developed septicaemia and required ventilation. Ultrasound examination of abdomen revealed bilateral hydronephrosis and multiple stones in left kidney. Percutaneous nephrostomy was performed on both sides. Subsequently, extracorporeal shock wave lithotripsy of left renal calculi was carried out. Right nephrostomy tube slipped out in January 2006; percutaneous nephrostomy was performed again. In June 2006, left ureteric antegrade stenting was performed and nephrostomy tube was removed. Currently, right kidney is drained by percutaneous nephrostomy and left kidney is drained by ureteric stent. This patient has indwelling urethral catheter.
Conclusion
It is possible that regular intermittent catheterisations along with anticholinergic medication right from the time of rehabilitation after this patient sustained paraplegia might have prevented the series of urological complications. Key components to successful management of external drainage of kidney in this patient are: [1] use of size 14 French pigtail catheter for long-term nephrostomy, [2] anchoring the catheter to skin to with Percufix catheter cuff to prevent accidental tug [3], replacing the nephrostomy dressing once a week by the same team in order to provide continuity of care, and [4] changing nephrostomy catheter every six months by a senior radiologist.
doi:10.1186/1757-1626-2-9335
PMCID: PMC2803994  PMID: 20062594
13.  Predictors of septic shock following anastomotic leak after major gastrointestinal surgery: An audit from a tertiary care institute 
Background:
Anastomotic leak is a serious complication after major gastrointestinal surgery and majority of deaths occur due to septic shock. Therefore, the early identification of risk factors of septic shock may help reduce the adverse outcomes.
Objective:
The aim of this audit was to determine the predictors of septic shock in patients with anastomotic leak after major gastrointestinal surgery.
Design:
Retrospective, audit.
Materials and Methods:
The patients admitted in the gastrosurgical intensive care unit ICU) of our institute between September 2009 and April 2012 with anastomotic leakage after surgery were identified. The ICU charts were retrieved from the database to identify the patients progressing to septic shock. A comparison of risk factors was made between the patients who developed septic shock (septic shock group) against the patients who did not (non-septic shock group).
Results:
The study sample comprised of 103 patients with anastomotic leak, of which 72 patients developed septic shock. The septic shock group had a higher APACHE II score, lower MAP, and higher HR at the time of ICU admission. They received greater transfusion of packed red blood cells during their ICU stay. Septic shock was more common after pancreaticojejunostomy and hepaticojejunostomy leaks.
Conclusion:
Presence of malignancy, chronic obstructive pulmonary disease (COPD), packed red blood cell transfusion, bacteremia, and hepaticojejunostomy or pancreaticojejunostomy leaks were independent predictors of mortality and length of ICU stay. To the best of our knowledge there are no available studies in the literature on the predictors of risk factors of septic shock in patients with anastomotic leakage.
doi:10.4103/0972-5229.120322
PMCID: PMC3841493  PMID: 24339642
Anastomotic leakage; post-leak sepsis; septic shock
14.  Survival Analysis of 314 Episodes of Sepsis in Medical Intensive Care Unit in University Hospital: Impact of Intensive Care Unit Performance and Antimicrobial Therapy 
Croatian medical journal  2006;47(3):385-397.
Aim
To evaluate epidemiology of sepsis in medical intensive care unit (ICU) in an university hospital, and the impact of ICU performance and appropriate empirical antibiotic therapy on survival of septic patients.
Methods
Observational, partly prospective study conducted over 6 years assessed all patients meeting the criteria for sepsis at ICU admission at the Sisters of Mercy Hospital in Zagreb. Clinical presentation of sepsis was defined according to 2001 International Sepsis Definitions Conference. Demographic data, admission category, source of infection, severity of sepsis, ICU or hospital stay and outcome, ICU performance, and appropriateness of empirical antibiotic therapy were analyzed.
Results
The analysis included 314 of 5022 (6.3%) patients admitted to ICU during the study period. There were 176 (56.1%) ICU survivors. At the ICU admission, sepsis was present in 100 (31.8%), severe sepsis in 89 (28.6%), and septic shock in 125 (39.8%) patients with mortality rates 17%, 33.7%, 72.1%, respectively. During ICU treatment, 244 (77.7%) patients developed at least one organ dysfunction syndrome. Of 138 (43.9%) patients who met the criteria for septic shock, 107 (75.4) were non-survivors (P<0.001). Factors associated with in-ICU mortality were acquisition of sepsis at another department (odds ratio [OR] 0.06; 95% confidence interval [CI], 0.02-0.19), winter season (OR 0.42; 0.20-0.89), limited mobility (OR 0.28; 0.14-0.59), ICU length of stay (OR 0.82; 0.75-0.91), sepsis-related organ failure assessment (SOFA) score on day 1 (OR 0.80; 0.72-0.89), history of global heart failure (OR 0.33; 0.16-0.67), chronic obstructive pulmonary disease (COPD)-connected respiratory failure (OR 0.50; 0.27-0.93), septic shock present during ICU treatment (OR 0.03; 0.01-0.10), and negative blood culture at admission (OR 2.60; 0.81-6.23). Microbiological documentation of sepsis was obtained in 235 (74.8%) patients. Urinary tract infections were present in 168 (53.5%) patients, followed by skin or soft tissue infections in 58 (18.5%) and lower respiratory tract infections in 44 (14.0%) patients. Lower respiratory tract as focus of sepsis was connected with worse outcome (P<0.001). Empirical antibiotic treatment was considered adequate in 107 (60.8%) survivors and 42 (30.4%) non-survivors. Patients treated with adequate empirical antibiotic therapy had significantly higher survival time in hospital (log-rank, P = 0.001).
Conclusion
The mortality rate of sepsis was unacceptably high. The odds for poor outcome increased with acquisition of sepsis at another department, winter season, limited mobility, higher SOFA score on day 1, history of chronic global heart failure, COPD-connected respiratory failure, and septic shock present during ICU treatment, whereas longer ICU length of stay, positive blood culture, and adequate empirical antibiotic therapy were protective factors.
PMCID: PMC2080418  PMID: 16758516
15.  The epidemiology of septic shock in French intensive care units: the prospective multicenter cohort EPISS study 
Critical Care  2013;17(2):R65.
Introduction
To provide up-to-date information on the prognostic factors associated with 28-day mortality in a cohort of septic shock patients in intensive care units (ICUs).
Methods
Prospective, multicenter, observational cohort study in ICUs from 14 French general (non-academic) and university teaching hospitals. All consecutive patients with septic shock admitted between November 2009 and March 2011 were eligible for inclusion. We prospectively recorded data regarding patient characteristics, infection, severity of illness, life support therapy, and discharge.
Results
Among 10,941 patients admitted to participating ICUs between October 2009 and September 2011, 1,495 (13.7%) patients presented inclusion criteria for septic shock and were included. Invasive mechanical ventilation was needed in 83.9% (n = 1248), inotropes in 27.7% (n = 412), continuous renal replacement therapy in 32.5% (n = 484), and hemodialysis in 19.6% (n = 291). Mortality at 28 days was 42% (n = 625). Variables associated with time to mortality, right-censored at day 28: age (for each additional 10 years) (hazard ratio (HR) = 1.29; 95% confidence interval (CI): 1.20-1.38), immunosuppression (HR = 1.63; 95%CI: 1.37-1.96), Knaus class C/D score versus class A/B score (HR = 1.36; 95%CI:1.14-1.62) and Sepsis-related Organ Failure Assessment (SOFA) score (HR = 1.24 for each additional point; 95%CI: 1.21-1.27). Patients with septic shock and renal/urinary tract infection had a significantly longer time to mortality (HR = 0.56; 95%CI: 0.42-0.75).
Conclusion
Our observational data of consecutive patients from real-life practice confirm that septic shock is common and carries high mortality in general ICU populations. Our results are in contrast with the clinical trial setting, and could be useful for healthcare planning and clinical study design.
doi:10.1186/cc12598
PMCID: PMC4056892  PMID: 23561510
16.  Pyelonephritis (acute) in non-pregnant women 
Clinical Evidence  2008;2008:0807.
Introduction
Pyelonephritis is usually caused by ascent of bacteria, most often Escherichia coli, from the bladder, and is more likely in people with structural or functional urinary tract abnormalities. The prognosis is good if pyelonephritis is treated appropriately, but complications include renal abscess, renal impairment, and septic shock.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of: oral antibiotic treatments for acute pyelonephritis in women with uncomplicated infection; antibiotic treatments in women admitted to hospital with complicated infection; inpatient versus outpatient management in women with uncomplicated infection; analgesia in uncomplicated acute pyelonephritis? We searched: Medline, Embase, The Cochrane Library and other important databases up to February 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 5 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: analgesics, inpatient management, intravenous antibiotics, non-opioids, non-steroidal anti-inflammatory drugs, oral antibiotics, outpatient management, urinary analgesics.
Key Points
Pyelonephritis is usually caused by ascent of bacteria from the bladder, most often Escherichia coli, and is more likely in people with structural or functional urinary tract abnormalities. The prognosis is good if pyelonephritis is treated appropriately, but complications include renal abscess, renal impairment, and septic shock.
Consensus is that oral antibiotics, given in the outpatient setting, are effective in non-pregnant women with uncomplicated pyelonephritis, although no placebo-controlled studies have been found. We don't know whether any one treatment regimen is more effective, or what the optimum duration of treatment is, although it may be sensible to continue treatment for at least 10 days.Broader spectrum antibiotics, such as quinolones, may be more effective compared with narrower spectrum antibiotics, such as ampicillin, amoxicillin, or co-trimoxazole, in areas where resistance to these is common.In the outpatient setting, we don't know whether intravenous antibiotics are more effective in non-pregnant women with uncomplicated pyelonephritis compared with oral regimens.
Intravenous antibiotics are considered effective in women admitted to hospital with uncomplicated pyelonephritis. We don't know which is the most effective intravenous antibiotic regimen, or the optimum duration of treatment.Combining intravenous plus oral antibiotics may be no more effective that oral antibiotics alone, but the evidence is weak.
We don't know whether inpatient treatment improves outcomes compared with outpatient treatment.
We found no evidence that simple analgesics ,NSAIDs, or urinary analgesics reduce pain from uncomplicated pyelonephritis. NSAIDs may worsen renal function and should be used in caution in women with pyelonephritis.
PMCID: PMC2907999  PMID: 19450332
17.  Risk factors and prognosis of critically ill cancer patients with postoperative acute respiratory insufficiency 
BACKGROUND:
This study aimed to investigate the risk factors and outcome of critically ill cancer patients with postoperative acute respiratory insufficiency.
METHODS:
The data of 190 critically ill cancer patients with postoperative acute respiratory insufficiency were retrospectively reviewed. The data of 321 patients with no acute respiratory insufficiency as controls were also collected. Clinical variables of the first 24 hours after admission to intensive care unit were collected, including age, sex, comorbid disease, type of surgery, admission type, presence of shock, presence of acute kidney injury, presence of acute lung injury/acute respiratory distress syndrome, acute physiologic and chronic health evaluation (APACHE II) score, sepsis-related organ failure assessment (SOFA), and PaO2/FiO2 ratio. Duration of mechanical ventilation, length of intensive care unit stay, intensive care unit death, length of hospitalization, hospital death and one-year survival were calculated.
RESULTS:
The incidence of acute respiratory insufficiency was 37.2% (190/321). Multivariate logistic analysis showed a history of chronic obstructive pulmonary diseases (P=0.001), surgery-related infection (P=0.004), hypo-volemic shock (P<0.001), and emergency surgery (P=0.018), were independent risk factors of postoperative acute respiratory insufficiency. Compared with the patients without acute respiratory insufficiency, the patients with acute respiratory insufficiency had a prolonged length of intensive care unit stay (P<0.001), a prolonged length of hospitalization (P=0.006), increased intensive care unit mortality (P=0.001), and hospital mortality (P<0.001). Septic shock was shown to be the only independent prognostic factor of intensive care unit death for the patients with acute respiratory insufficiency (P=0.029, RR: 8.522, 95%CI: 1.243–58.437, B=2.143, SE=0.982, Wald=4.758). Compared with the patients without acute respiratory insufficiency, those with acute respiratory insufficiency had a shortened one-year survival rate (78.7% vs. 97.1%, P<0.001).
CONCLUSION:
A history of chronic obstructive pulmonary diseases, surgery-related infection, hypovolemic shock and emergency surgery were risk factors of critically ill cancer patients with postoperative acute respiratory insufficiency. Septic shock was the only independent prognostic factor of intensive care unit death in patients with acute respiratory insufficiency. Compared with patients without acute respiratory insufficiency, those with acute respiratory insufficiency had adverse short-term outcome and a decreased one-year survival rate.
doi:10.5847/wjem.j.issn.1920-8642.2013.01.008
PMCID: PMC4129891  PMID: 25215091
Acute respiratory insufficiency; Risk factors; Prognosis; Critical illness; Postoperative care; Septic shock; Chronic obstructive pulmonary disease; Survival
18.  Association between Mannose-Binding Lectin Deficiency and Septic Shock following Acute Pyelonephritis Due to Escherichia coli▿  
Clinical and Vaccine Immunology  2007;14(3):256-261.
Structural and promoter MBL2 gene polymorphisms responsible for low MBL levels are associated with increased risk of infection. The objective of this study was to assess the possible association between polymorphisms of the MBL2 gene and the incidence of septic shock and bacteremia in patients with acute pyelonephritis due to Escherichia coli. The study included 62 female patients with acute pyelonephritis due to E. coli who required hospital admission, as well as 133 healthy control subjects. Six single-nucleotide polymorphisms (−550 G/C, −221 C/G, +4 C/T, codon 52 CGT/TGT, codon 54 GGC/GAC, and codon 57 GGA/GAA) in the MBL2 gene were genotyped by using a sequence-based typing technique. No significant differences were observed in the frequencies for low-expression MBL2 genotypes (O/O and LXA/O) between patients with acute pyelonephritis and healthy controls. Patients with acute pyelonephritis and septic shock had a higher incidence of low-expression MBL2 genotypes than patients with acute pyelonephritis without septic shock (odds ratio = 9.019, 95% confidence interval = 1.23 to 65.93; P = 0.03). No association was found between bacteremic acute pyelonephritis and low-expression MBL2 genotypes. We found that low-expression MBL2 genotypes predispose to septic shock but not to bacteremia in patients with E. coli-induced acute pyelonephritis. Determination of MBL2 polymorphisms could be useful for assessing the risk of septic shock in women undergoing acute pyelonephritis.
doi:10.1128/CVI.00400-06
PMCID: PMC1828851  PMID: 17202308
19.  A high angiopoietin-2/angiopoietin-1 ratio is associated with a high risk of septic shock in patients with febrile neutropenia 
Critical Care  2013;17(4):R169.
Introduction
Endothelial barrier breakdown is a hallmark of septic shock, and proteins that physiologically regulate endothelial barrier integrity are emerging as promising biomarkers of septic shock development. Patients with cancer and febrile neutropenia (FN) present a higher risk of sepsis complications, such as septic shock. Nonetheless, these patients are normally excluded or under-represented in sepsis biomarker studies. The aim of our study was to validate the measurement of a panel of microvascular permeability modulators as biomarkers of septic shock development in cancer patients with chemotherapy-associated FN.
Methods
This was a prospective study of diagnostic accuracy, performed in two distinct in-patient units of a university hospital. Levels of vascular endothelial growth factor A (VEGF-A), soluble fms-like tyrosine kinase-1 (sFlt-1) and angiopoietin (Ang) 1 and 2 were measured after the onset of neutropenic fever, in conditions designed to mimic the real-world use of a sepsis biomarker, based on our local practice. Patients were categorized based on the development of septic shock by 28 days as an outcome.
Results
A total of 99 consecutive patients were evaluated in the study, of which 20 developed septic shock and 79 were classified as non-complicated FN. VEGF-A and sFlt-1 levels were similar between both outcome groups. In contrast, Ang-2 concentrations were increased in patients with septic shock, whereas an inverse finding was observed for Ang-1, resulting in a higher Ang-2/Ang-1 ratio in patients with septic shock (5.29, range 0.58 to 57.14) compared to non-complicated FN (1.99, range 0.06 to 64.62; P = 0.01). After multivariate analysis, the Ang-2/Ang-1 ratio remained an independent factor for septic shock development and 28-day mortality.
Conclusions
A high Ang-2/Ang-1 ratio can predict the development of septic shock in cancer patients with febrile neutropenia.
doi:10.1186/cc12848
PMCID: PMC4056795  PMID: 23915833
20.  Epidemiological and Clinical Characteristics of Community-Acquired Severe Sepsis and Septic Shock: A Prospective Observational Study in 12 University Hospitals in Korea 
Journal of Korean Medical Science  2012;27(11):1308-1314.
A prospective multicenter observational study was performed to investigate the epidemiology and outcomes of community-acquired severe sepsis and septic shock. Subjects included 1,192 adult patients admitted to the 22 participating intensive care units (ICUs) of 12 university hospitals in the Korean Sepsis Registry System from April, 2005 through February, 2009. Male accounted for 656 (55%) patients. Mean age was 65.0 ± 14.2 yr. Septic shock developed in 740 (62.1%) patients. Bacteremia was present in 422 (35.4%) patients. The 28-day and in-hospital mortality rates were 23.0% and 28.0%, respectively. Men were more likely to have comorbid illnesses and acute organ dysfunctions, and had higher mortality and clinical severity compared to women. While respiratory sources of sepsis were common in men, urinary sources were predominant in women. In the multivariate logistic regression analysis, cancer (odds ratio 1.89; 95% confidence interval 1.13-3.17), urinary tract infection (0.25; 0.13-0.46), APACHE II score (1.05; 1.02-1.09), SOFA score on day 1 (1.13; 1.06-1.21) and metabolic dysfunction (2.24, 1.45-3.45) were independent clinical factors for gender-related in-hospital mortality. This study provided epidemiological and clinical characteristics of community-acquired severe sepsis and septic shock in ICUs in Korea, and demonstrated the impact of clinical factors on gender difference in mortality.
doi:10.3346/jkms.2012.27.11.1308
PMCID: PMC3492663  PMID: 23166410
Epidemiology; Severe Sepsis; Septic Shock; Mortality; Risk Factor; Gender
21.  A Giant Case of Pyonephrosis Resulting from Nephrolithiasis 
Case Reports in Urology  2014;2014:161640.
Pyonephrosis is an uncommon disease that is associated with suppurative destruction of the renal parenchyma in adults. Upper urinary tract infection and obstruction play a role in its etiology. Immunosuppression from medications (steroids), diseases (diabetes mellitus, AIDS), and anatomic variations (pelvic kidney, horseshoe kidney) may also be risk factors for pyonephrosis. Fever, shivering, and flank pain are frequent clinical symptoms. On physical examination, a palpable abdominal mass may be associated with the hydronephrotic kidney. Septic shock and death can occur if the disorder is not treated with urgent surgery. After the acute phase, most patients are treated with nephrectomy. In this paper, we share the etiology, clinical features, diagnosis and treatment of pyonephrosis using the background of a case with giant pyonephrosis developing due to a kidney stone, the most common cause of upper urinary tract obstruction.
doi:10.1155/2014/161640
PMCID: PMC4106088  PMID: 25105051
22.  Simultaneous vs staged treatment of urolithiasis in patients undergoing radical prostatectomy 
AIM: To assess the outcomes of men treated for urolithiasis at the time of radical prostatectomy.
METHODS: From 1991 to 2010, 22 patients were retrospectively identified who were treated simultaneously (n = 10) at radical prostatectomy, or (n = 12) within 120 d prior to prostatectomy, for urolithiasis. Clinical characteristics were reviewed including: type of prostatectomy and stone surgery, location and amount of stone burden, perioperative change in hemoglobin and creatinine, stent frequency, total hospital d, stone-free rates, additional stone procedures and complications. Long-term functional outcomes including stress urinary incontinence and bladder neck contracture were reported. Differences between cohorts (simultaneous vs staged treatment) were assessed.
RESULTS: Among men undergoing radical prostatectomy, primary stone procedures included 12 ureteroscopy, 6 shock wave lithotripsy, 2 open nephrolithotomy and 2 percutaneous nephrolithotomy. In staged shock wave lithotripsy there were 4 complications and 3 additional procedures vs 1 (P = 0.5) and 0 (P = 0.2) in the simultaneous cohort. Meanwhile in staged ureteroscopy there were 5 complications and 1 additional procedure vs 1 (P = 0.2) and 1 (P = 0.9) in the simultaneous cohort. Additional procedures for residual stones was greater among patients with asymptomatic upper tract calculi 3 (60%) relative to patients with symptomatic stones 2 (13%; P = 0.02). Likewise, patients with proximal or multiple calculi had a greater total hospital days 5.5 vs 4.1 (P = 0.04), additional procedures 6 vs 0 (P = 0.04) and lower stone-free rates 39% vs 89% (P = 0.02) relative to men with distal stones. Finally, there was no difference in the incidence of bladder neck contracture (P = 0.4) or stress urinary incontinence (P = 0.7) between cohorts.
CONCLUSION: Ureteroscopic treatment of symptomatic distal urolithiasis at radical prostatectomy appears to be safe and efficacious with a low rate of adverse postoperative outcomes.
doi:10.12998/wjcc.v2.i11.698
PMCID: PMC4233425  PMID: 25405194
Urolithiasis; Kidney stone; Prostate cancer; Radical prostatectomy
23.  Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008 
Intensive Care Medicine  2007;34(1):17-60.
Objective
To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, “Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock,” published in 2004.
Design
Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding.
Methods
We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation [1] indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations [2] indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations.
Results
Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7–10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure ≥ 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7–9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D).
Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B).
Conclusion
There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.
doi:10.1007/s00134-007-0934-2
PMCID: PMC2249616  PMID: 18058085
Sepsis; Severe sepsis; Septic shock; Sepsis syndrome; Infection; GRADE; Guidelines; Evidence-based medicine; Surviving Sepsis Campaign; Sepsis bundles
24.  Group B streptococcus cystitis presenting in a diabetic patient with a massive abdominopelvic abscess: a case report 
Introduction
Streptococcus agalactiae or group B streptococcus is a Gram-positive pathogen that is typically associated with neonatal disease and infection in pregnant women. Group B streptococcus also causes invasive infections in non-pregnant adults including urinary tract infections. The spectrum of urinary tract infections caused by group B streptococcus includes cystitis, pyelonephritis, urosepsis and asymptomatic bacteriuria, which is particularly common among elderly individuals. A rare form of invasive group B streptococcus infection in adults is secondary abscess. Here, we present the first reported case of a patient who developed an unusual, massive abdominopelvic abscess secondary to acute group B streptococcus urinary tract infection.
Case presentation
A 46-year-old African-American woman presented to the University Emergency Department complaining of urinary tract infection symptoms and severe abdominal pain. Diagnostic imaging by transvaginal ultrasound and computed tomography revealed a massive peripherally-enhancing, low-attenuating fluid collection within her pelvis. The patient’s abdominopelvic abscess was drained by ultrasound-guided drainage and this yielded a septic aspirate that was culture positive for abundant S. agalactiae. A recent history of urinary tract infection symptoms in the patient suggested that her abscess developed secondary to cystitis. Complete resolution of the abscess as a favorable outcome was achieved in this case following surgical drainage and appropriate antimicrobial therapy.
Conclusion
Acute bacterial urinary tract infection leading to an abdominopelvic abscess has not previously been reported in the literature. This case report defines a new disease etiology associated with acute streptococcal cystitis and it will be of interest in cases of urinary tract infections where there is an association with abdominal and/or pelvic pain. A brief review of the literature on unusual secondary abscesses due to group B streptococcus is provided alongside this case to highlight the clinical significance and prognoses of these rare infections. Finally, this case emphasizes the requirement to distinguish unusual etiologies of pyogenic abscesses in order to guide successful clinical management and to treat patients with antibiotics active against the causal organism.
doi:10.1186/1752-1947-6-237
PMCID: PMC3443647  PMID: 22883571
Abscess; Cystitis; Group B streptococcus; Streptococcus agalactiae; Urinary tract infection
25.  Circulating immune parameters predicting the progression from hospital-acquired pneumonia to septic shock in surgical patients 
Critical Care  2005;9(6):R662-R669.
Introduction
Hospital-acquired pneumonia after surgery is one of the major causes of septic shock. The excessive inflammatory response appears to be responsible for the increased susceptibility to infections and subsequent sepsis. The primary aim of this study was to investigate immune parameters at the onset of pneumonia, before the development of subsequent septic shock. The secondary aim was to investigate the usefulness of these immune parameters in predicting progression from hospital-acquired pneumonia to septic shock.
Methods
This propective clinical study included 76 patients with the diagnosis of hospital-acquired pneumonia. Approval was obtained from the local institutional ethics committee and relatives of the patients gave informed consent. Of the 76 patients, 29 subsequently developed septic shock. All patients were included within 4 h of establishing the diagnosis of hospital-acquired pneumonia (first collection of blood samples and the analysis of immune mediators). In addition, we defined early (within 12 h of onset of septic shock) and late (within 72 to 96 h of onset) stages of septic shock for the collection of blood samples and the analysis of immune mediators. The immune parameters tumor necrosis factor-α, IL-1β, IL-6, IL-8 and IL-10 as well as the endothelial leucocyte adhesion molecule were analyzed.
Results
In the pneumonia group with subsequent septic shock, levels of IL-1β, IL-6, IL-8 and IL-10 were significantly increased before the onset of septic shock compared to patients without subsequent septic shock. This progression was best predicted by IL-1β, IL-6, IL-8 and IL-10 (area under the curve ≥ 0.8).
Conclusion
At the onset of hospital-acquired pneumonia, a significant relevant systemic cytokine mediated response had already been initiated. It might, therefore, be possible to identify patients at risk for septic shock with these predictive markers during early pneumonia. In addition, immune modulating therapy might be considered as adjuvant therapy.
doi:10.1186/cc3826
PMCID: PMC1414040  PMID: 16280065

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