Validation of the new Sepsis-3 definitions: proposal for improvement in early risk identification.

OBJECTIVES: Sepsis-3 definitions generated controversies regarding their general applicability. The Sepsis-3 Task Force outlined the need for validation with emphasis on the quick Sequential Organ Failure Assessment (qSOFA) score. This was done in a prospective cohort from a different healthcare setting. METHODS: Patients with infections and at least two signs of systemic inflammatory response syndrome (SIRS) were analysed. Sepsis was defined as total SOFA ≥2 outside the intensive care unit (ICU) or as an increase of ICU admission SOFA ≥2. The primary endpoints were the sensitivity of qSOFA outside the ICU and sepsis definition both outside and within the ICU to predict mortality. RESULTS: In all, 3346 infections outside the ICU and 1058 infections in the ICU were analysed. Outside the ICU, respective mortality with ≥2 SIRS and qSOFA ≥2 was 25.3% and 41.2% (p <0.0001); the sensitivities of qSOFA and of sepsis definition to predict death were 60.8% and 87.2%, respectively. This was 95.9% for sepsis definition in the ICU. The sensitivity of qSOFA and of ≥3 SIRS criteria for organ dysfunction outside the ICU was 48.7% and 72.5%, respectively (p <0.0001). Misclassification outside the ICU with the 1991 and Sepsis-3 definitions into stages of lower severity was 21.4% and 3.7%, respectively (p <0.0001) and 14.9% and 3.7%, respectively, in the ICU (p <0.0001). Adding arterial pH ≤7.30 to qSOFA increased sensitivity for prediction of death to 67.5% (p 0.004). CONCLUSIONS: Our analysis positively validated the use of SOFA score to predict unfavourable outcome and to limit misclassification into lower severity. However, qSOFA score had inadequate sensitivity for early risk assessment.

Improving outcomes of severe infections by multidrug-resistant pathogens with polyclonal IgM-enriched immunoglobulins.

The emergence of infections by multidrug-resistant (MDR) Gram-negative bacteria, which is accompanied by considerable mortality due to inappropriate therapy, led to the investigation of whether adjunctive treatment with one polyclonal IgM-enriched immunoglobulin preparation (IgGAM) would improve outcomes. One hundred patients in Greece with microbiologically confirmed severe infections by MDR Gram-negative bacteria acquired after admission to the Intensive Care Unit and treated with IgGAM were retrospectively analysed from a large prospective multicentre cohort. A similar number of patient comparators well-matched for stage of sepsis, source of infection, appropriateness of antimicrobials and co-morbidities coming from the same cohort were selected. All-cause 28-day mortality was the primary end point; mortality by extensively drug-resistant (XDR) pathogens and time to breakthrough bacteraemia were the secondary end points. Fifty-eight of the comparators and 39 of the IgGAM-treated cases died by day 28 (p 0.011). The OR for death under IgGAM treatment was 0.46 (95% CI 0.26-0.85). Stepwise regression analysis revealed that IgGAM was associated with favourable outcome whereas acute coagulopathy, cardiovascular failure, chronic obstructive pulmonary disease and chronic renal disease were associated with unfavourable outcome. Thirty-nine of 62 comparators (62.9%) were infected by XDR Gram-negative bacteria and died by day 28 compared with 25 of 65 cases treated with IgGAM (38.5%) (p 0.008). Median times to breakthrough bacteraemia were 4 days and 10 days, respectively (p <0.0001). Results favour the use of IgGAM as an adjunct to antimicrobial treatment for the management of septic shock caused by MDR Gram-negative bacteria. A prospective randomized trial is warranted.

Hypokalemia-induced cardiac arrest in a Duchenne muscular dystrophy patient.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a progressive myopathic disorder, inherited as X-linked recessive traits, in which muscle weakness is the primary symptom. Correlation between DMD and hypokalemia is reported in only three case reports. Recent investigations have focused on the nutritional management of patients with DMD. However, there are no data regarding recommendations on potassium intake. Description of case: We report the case of a 15-year-old male patient with DMD, who developed sudden cardiac arrest following severe hypokalemia (K: 1.3 mEq/L) during a lower respiratory tract infection. Hypokalemia was gradually corrected with intravenous potassium chloride. The patient, after a prolonged hospitalization due to hypoxic encephalopathy, was discharged from the Intensive Care Unit (ICU) on mechanical ventilation. CONCLUSION: Severe hypokalemia is a rare complication of DMD, with potentially lethal consequences. Therefore, in patients with DMD, potassium levels should be closely monitored and adjusted with appropriate diet or potassium supplements as needed. Hippokratia 2016, 20(2): 163-165.

Prospective evaluation of post-implantation inflammatory response after EVAR for AAA: influence on patients' 30 day outcome.

OBJECTIVES: The aim was to prospectively evaluate post-implantation syndrome (PIS) after elective endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs) and to investigate its association with clinical and laboratory parameters and the clinical outcome of the patients. METHODS: From January 2010 till June 2013, 214 consecutive patients treated electively by EVAR for AAA were prospectively included. PIS was defined according to systemic inflammatory response syndrome criteria. Adverse events included any major adverse cardiovascular events (MACE), acute renal failure, re-admission and death from any cause. RESULTS: PIS was diagnosed in 77 (34%) patients. Pre-operative white blood cell (WBC) count values (p < .001), endograft material (polyester) (p < .001), and heart failure (p = .03) were independent predictors of PIS. Mean post-operative temperature (p < .001), length of hospital (p < .001) and intensive care unit (p = .008) stay, as well as maximum post-operative WBC count (p < .001) and hs-CRP values (p < .001) were significantly higher in the PIS group. Post-operative hs-CRP (p = .001) and duration of fever (p = .02) independently predicted the occurrence of MACE. Post-operative hs-CRP (p = .004), maximum temperature (p = .03), and the presence of PIS (p = .01) were independent predictors of an adverse event during the first 30 days. A threshold of post-operative hs-CRP value of 125 mg/L was highly associated with the occurrence of MACE, with a sensitivity of 82% and specificity of 75%. CONCLUSIONS: A systematic inflammatory response is observed in a significant number of patients after EVAR. The type of endograft material seems to play a significant role in this inflammatory process. The intensity of inflammation, as assessed mainly by the post-operative hs-CRP values, correlates with the presence of a cardiovascular or any other adverse event during the first 30 days after the procedure.

Early ischaemic preconditioning of spinal cord enhanced the binding profile of heat shock protein 70 with neurofilaments and promoted its nuclear translocation after thoraco-abdominal aortic occlusion in pigs.

OBJECTIVE(S): Heat shock protein 70 (Hsp70) is detected in substantial amounts in normal neurons and this basal content may protect a cell against harmful conditions without the need for additional synthesis. Herein, we investigate the potential protective role of these basal levels of Hsp70, in an early ischaemic preconditioning (IPC) experimental model, suggesting a possible role of this protein as a first window of protection. DESIGN, MATERIAL AND METHODS: Forty-two pigs were used in an experimental thoraco-abdominal aortic occlusion model. Twelve animals (two groups) were used for neurological evaluation. The remaining 30 animals (five groups) were used for immunoprecipitation and immunohistochemical studies. These were performed to study the binding relationship of Hsp70/cytoskeleton elements and the cellular distribution of Hsp70, respectively. RESULTS: The IPC + ischaemia-group showed significant better neurologic scores compared with those of the ischaemia group, indicating a protective role for IPC (P = 0.003). The immunoprecipitations demonstrated that early IPC increased significantly the binding profile of Hsp70/neurofilaments (P = 0.025). In addition, translocation of Hsp70 into the nucleus was observed, which was conserved until the sustained ischaemia. CONCLUSIONS: These results indicate that Hsp70 may have an important role in early IPC of the spinal cord, by protecting neurofilaments and by ensuring the functionality and the integrity of the nucleus, at the time the intensive insult begins.

Procalcitonin as an early indicator of outcome in sepsis: a prospective observational study.

This study explores the role of procalcitonin (PCT) in predicting the outcome of sepsis. In a prospective multicentre observational investigation, blood was sampled within 24 h of onset of sepsis in 1156 hospitalised patients; 234 were in the intensive care unit (ICU) at the point of presentation of sepsis while 922 were not. PCT was estimated in serum by the ultrasensitive Kryptor assay in a double-blinded fashion. Among patients outside the ICU, mortality was 8% in those with PCT ≤0.12 ng/mL but 19.9% in those with PCT >0.12 ng/mL [P<0.0001, odds ratio (OR) for death: 2.606; 95% confidence interval (CI): 1.553-4.371]. Among patients whose sepsis presented in ICU, mortality was 25.6% in those with PCT ≤0.85 ng/mL but 45.3% in those with PCT >0.85 ng/mL (P=0.002; OR for death: 2.404; 95% CI: 1.385-4.171). It is concluded that PCT cut-off concentrations can contribute to predicting the outcome of sepsis and might be of particular value in identifying patients who would benefit from ICU admission.

Acute lung injury probably associated with infusion of propofol emulsion.

We present a case of acute lung injury associated with propofol infusion in a mechanically ventilated patient with intracerebral haemorrhage. Diagnosis was based on the exclusion of other risk factors inducing acute lung injury and on the clinical improvement after discontinuation of the propofol emulsion. Laboratory data such as the increase in total phospholipids, neutral lipids and free fatty acids in the broncho-alveolar lavage fluid, the remarkably high percentage of alveolar macrophages including fat droplets and the similar lipid composition of propofol and broncho-alveolar lavage fluid support the relationship between propofol and acute lung injury.

Acute massive rhabdomyolysis due to prolonged inhalation of liquid gas.

A very rare case of non-fatal acute massive rhabdomyolysis caused by unintentional prolonged inhalation of liquid gas (consisting of butane and propane) in a previously healthy adult is presented. The immediate diagnosis and intensive symptomatic therapy prevented any other severe complications of rhabdomyolysis, and the patient made a complete recovery without any sequelae.

Effect of the prone position on patients with hydrostatic pulmonary edema compared with patients with acute respiratory distress syndrome and pulmonary fibrosis.

This study examined the effect of the prone position on mechanically ventilated patients with hydrostatic pulmonary edema (HPE). Eight patients with acute HPE and mechanically ventilated in the prone position (Group 1) were studied. Six patients with acute HPE and mechanically ventilated in the supine position (Group 2), 20 patients with ARDS (Group 3), and 5 patients with pulmonary fibrosis (PF) (Group 4) served as control patients. Patients with HPE, who after being mechanically ventilated for at least 6 h needed an FI(O(2)) >/= 0.6 to achieve an Sa(O(2)) of approximately 90%, and did not respond to recruitment maneuvers, were turned to the prone position. Parameters of oxygenation, lung mechanics, and hemodynamics were determined in both the supine and prone positions. All patients with HPE exhibited improvement of oxygenation when they were placed in the prone position. The Pa(O(2))/FI(O(2)) ratio increased from 72 +/- 16 in the supine position to 208 +/- 61 after 6 h in the prone position (p < 0.001); the rise in Pa(O(2)) was persistent, without detrimental effect on hemodynamics. Fifteen of 20 patients with ARDS (75%) improved oxygenation when in the prone position. The Pa(O(2))/FI(O(2)) ratio increased from 83 +/- 14 in the supine position to 189 +/- 34 after 6 h in the prone position (p < 0.001). In contrast, 5 of 20 patients with ARDS (25%) and none of the patients with PF responded favorably to prone positioning. Patients with HPE and early ARDS responded better to prone positioning than did patients with late ARDS and PF. Patients with HPE and ventilated in the supine position had a lower Pa(O(2))/FI(O(2)) ratio and the duration of mechanical ventilation was longer compared with that of patients in the prone position. Our results show that the prone position may be a useful maneuver in treating patients with severe hypoxemia due to pulmonary edema. The presence of pulmonary edema, as in early ARDS and HPE predicts a beneficial effect of the prone position on gas exchange. In contrast, the presence of fibrosis, as in late ARDS and pulmonary fibrosis, predisposes to nonresponsiveness to prone positioning.

Symptomatic deep venous thrombosis of the lower limb.

BACKGROUND: Deep vein thrombosis (DVT) is a common problem in clinical practice causing severe complications. In this retrospective study, the distribution and extent of DVT in the lower limb in symptomatic patients were evaluated. Certain risk factors were also investigated. METHODS: The venograms of 187 symptomatic individuals (postoperative, medical, and out-patient) with suspected DVT and symptoms having been present for less than 6 days, were reviewed. Seventy-seven limbs of 76 patients had DVT. Twenty-seven were male (age range 14-82 years, mean 57) and 49 female (age range 12-82, mean 56). RESULTS: Age over 40 years and gender (female) were significant predisposing factors, (Z = 4.23, p < 0.001 and Z = 2.19, p < 0.05 respectively). Isolated calf DVT alone was the most common pattern (46%, 36 of 77 limbs), and no difference was seen between postoperative and medical patients (chi 2-test, p = 0.7). Postoperative DVT was found in 29 (38%) limbs. Prophylaxis with LMWH had been given in only 15 of them (52%). No difference was seen in the distribution and extent of thrombosis in relation to the prophylaxis with LMWH (chi 2-test, p = 0.34). CONCLUSIONS: Identification of the predisposing factors may enable us to distinguish patients at high risk of developing DVT. The majority of the thrombi commenced in the calf veins and thus meticulous investigation of these veins in symptomatic patients with suspected DVT is necessary.