Cytokine patterns in critically ill patients undergoing percutaneous tracheostomy.

The inflammatory response to acute injury among humans has proved difficult to study due to the significant heterogeneity encountered in actual patients. We set out to characterize the immune response to a model injury with reduced heterogeneity, a tracheostomy, among stable critical care patients, using a broad cytokine panel and clinical data. Twenty-three critical care patients undergoing percutaneous bedside tracheostomies were recruited in a medical intensive care unit. Blood samples were collected at five intervals during 24-h peri-procedure. Patients were followed-up for 28 days for clinical outcomes. There were no statistically significant changes in any of the cytokines between the five time-points when studied as a whole cohort. Longitudinal analysis of the cytokine patterns at the individual patient level with a clustering algorithm showed that, notwithstanding the significant heterogeneity observed, the patients' cytokine responses can be classified into three broad patterns that show increasing, decreasing or no major changes from the baseline. This analytical approach also showed statistically significant associations between cytokines, with those most likely to be associated being interleukin (IL)-6, granulocyte colony-stimulating factor (GCSF) and ferritin, as well as a strong tri-way correlation between GCSF, monocyte chemoattractant protein 1 (MCP1) and macrophage inflammatory protein-1ß (MIP1ß). In conclusion, in this standard human model of soft tissue injury, by applying longitudinal analysis at the individual level, we have been able to identify the cytokine patterns underlying the seemingly random, heterogeneous patient responses. We have also identified consistent cytokine interactions suggesting that IL-6, GCSF, MCP1 and MIP1ß are the cytokines most probably driving the immune response to this injury.

Prognosis of patients with rheumatic diseases admitted to intensive care.

Variable mortality rates have been reported for patients with rheumatic diseases admitted to an intensive care unit (ICU). Due to the absence of appropriate control groups in previous studies, it is not known whether the presence of a rheumatic disease constitutes a risk factor. Moreover, the accuracy of the Acute Physiology and Chronic Health Evaluation II (APACHE II) score for predicting outcome in this group of patients has been questioned. The primary goal of this study was to compare outcome of patients with rheumatic diseases admitted to a medical ICU to those of controls. The records of all patients admitted between 1 April 2003 and 30 June 2014 (n=4020) were screened for the presence of a rheumatic disease during admission (n=138). The diagnosis of a rheumatic disease was by standard criteria for these conditions. An age- and gender-matched control group of patients without a rheumatic disease was extracted from the patient population in the database during the same period (n=831). Mortality in ICU, in hospital and after 180 days did not differ significantly between patients with and without rheumatic diseases. There was no difference in the performance of the APACHE II score for predicting outcome in patients with rheumatic diseases and controls. This score, as well as a requirement for the use of inotropes or vasopressors, accurately predicted hospital mortality in the group of patients with rheumatic diseases. In conclusion, patients with a rheumatic condition admitted to intensive care do not do significantly worse than patients without such a disease.

The role of Vitamin B12 in the critically ill--a review.

Vitamin B12 is an essential micronutrient, as humans have no capacity to produce the vitamin and it needs to be ingested from animal proteins. The ingested Vitamin B12 undergoes a complex process of absorption and assimilation. Vitamin B12 is essential for cellular function. Deficiency affects 15% of patients older than 65 and results in haematological and neurological disorders. Low levels of Vitamin B12 may also be an independent risk factor for coronary artery disease. High levels of Vitamin B12 are associated with inflammation and represent a poor outlook for critically ill patients. Treatment of Vitamin B12 deficiency is simple, but may be lifelong.

Successful introduction of a daily checklist to enhance compliance with accepted standards of care in the medical intensive care unit.

We introduced a simple checklist to act as an aid to memory for our junior medical staff to ensure that every patient in the intensive care unit (ICU) received every appropriate element of a bundle of care every day. The checklist was developed in consultation with our junior doctors and was designed to be completed every morning for every patient by the junior doctor reviewing the patient. The completed checklist was then checked again by the attending intensivist on the main daily ward round to ensure all the appropriate elements of the checklist had been applied to the patient. It was also noted each day which of the elements of the checklist had been forgotten and was therefore prompted to be completed by use of the checklist. Of the 75 patients surveyed there were 99 occasions, in 48 patients, when the checklist detected a forgotten element of the bundle of care (i.e. in 64% of patients). There was a decrease in the incidence of missed elements of the bundle of care the longer the patient stayed in the ICU. Types of missed elements varied with the duration of the ICU stay. We found that the introduction of a simple checklist, developed in collaboration with the junior medical staff who would be using the checklist every day in the ICU, resulted in the detection and correction of missed elements of a bundle of care we had previously introduced in the ICU.

Increased rates of intensive care unit admission in patients with Mycoplasma pneumoniae: a retrospective study.

Mycoplasma pneumoniae is a leading cause of respiratory disease. In the Intensive Care Unit (ICU) setting M. pneumoniae is not considered a common pathogen. In 2010-13 an epidemic of M. pneumoniae-associated infections was reported and we observed an increase of M. pneumoniae patients admitted to ICU. We analysed the cohort of all M. pneumoniae-positive patients' admissions during 2007 to 2012 at the Hadassah-Hebrew University Medical Centre (a 1100-bed tertiary medical centre). Mycoplasma pneumoniae diagnosis was made routinely using PCR on throat swabs and other respiratory samples. Clinical parameters were retrospectively extracted. We identified 416 M. pneumoniae-infected patients; of which 68 (16.3%) were admitted to ICU. Of these, 48% (173/416) were paediatric patients with ICU admission rate of 4.6% (8/173). In the 19- to 65-year age group ICU admission rate rose to 18% (32/171), and to 38.8% (28/72) for patients older than 65 years. The mean APACHE II score on ICU admission was 20, with a median ICU stay of 7 days, and median hospital stay of 11.5 days. Of the ICU-admitted patients, 54.4% (37/68) were mechanically ventilated upon ICU admission. In 38.2% (26/68), additional pathogens were identified mostly later as secondary pathogens. A concomitant cardiac manifestation occurred in up to 36.8% (25/68) of patients. The in-hospital mortality was 29.4% (20/68) and correlated with APACHE II score. Contrary to previous reports, a substantial proportion (16.3%) of our M. pneumoniae-infected patients required ICU admission, especially in the adult population, with significant morbidity and mortality.

Does high-dose vasopressor therapy in medical intensive care patients indicate what we already suspect?

PURPOSE: This study was conducted to determine the association between vasopressor requirement and outcome in medical intensive care patients in an environment where treatment is not withdrawn. MATERIALS AND METHODS: This was an observational study of patients in the medical intensive care unit (ICU) over a period of 18 months to determine the correlation between vasopressor requirement and mortality. Outcome was determined for all medical ICU patients, for patients receiving "low dose" (<40 µg/min) vasopressors (noradrenaline and/or adrenaline) or "high dose" (≥ 40 µg/min) vasopressors. Receiver operator characteristic curves were constructed for ICU and hospital mortality and high-dose vasopressor use. High-dose vasopressor use as an independent predictor for ICU and hospital mortality was also determined by multiple logistic regression analysis. RESULTS: Patients receiving high-dose noradrenaline at any time during their ICU admission had an 84.3% mortality in ICU and 90% in hospital. The receiver operator characteristic curves for high-dose vasopressors had an area under the curve of 0.799 for ICU mortality and 0.779 for hospital mortality. High-dose vasopressor was an independent predictor of ICU mortality, with an odds ratio of 5.1 (confidence interval, 2.02-12.9; P = .001), and of hospital mortality, with an odds ratio of 3.82 (confidence interval 1.28-11.37; P = .016). CONCLUSIONS: The requirement for high-dose vasopressor therapy at any time during ICU admission was associated with a very high mortality rate in the ICU and the hospital.

Increased Vitamin B12 levels are associated with mortality in critically ill medical patients.

BACKGROUND & AIMS: We describe an observational study in critically ill medical patients showing the association between serum Vitamin B12 levels measured on or near admission and the outcome in these patients. METHODS: We used the database of patients admitted to the Medical Intensive Care Unit (MICU) at the Hadassah-Hebrew University Medical Center in Jerusalem, Israel, to analyze associations between patient demographics, background, diagnoses and serum Vitamin B12 levels with hospital and 90 day outcomes. RESULTS: Higher mean Vitamin B12 levels were found in patients who did not survive their hospital stay (1719 pg/ml vs 1003 pg/ml, p < 0.01). Those who had died by 90 days after admission to the MICU also had higher Vitamin B12 levels than survivors (1593 pg/ml vs 990 pg/ml). Regression analysis showed that elevated Vitamin B12 levels were associated with increased 90 day mortality, even after controlling for other variables. Survival analysis also showed an increased mortality rate in patients with Vitamin B12 levels over 900 pg/ml (p < 0.0002). CONCLUSIONS: Our data show that high serum Vitamin B12 levels are associated with increased mortality in critically ill medical patients. We suggest that Vitamin B12 levels should be included in the work-up of all medical intensive care patients, particularly those with a chronic health history and increased severity of illness.

Non-invasive Mechanical Ventilation Enhances Patient Autonomy in Decision-Making Regarding Chronic Ventilation.

OBJECTIVE: Patients with respiratory failure due to progressive muscle weakness often require chronic ventilatory support, but many do not make decisions regarding ventilation prior to a crisis. We studied the use of non-invasive ventilation as a tool to enable communication and facilitate decision-making regarding chronic ventilation. METHODS: Patients with profound muscle weakness and acute respiratory failure, were supported or weaned by non-invasive positive or negative pressure ventilation. The patients were then interviewed and their informed autonomous decisions were used to plan their future management. RESULTS: Non-invasive ventilation could be used safely to support patients with acute respiratory failure until decisions regarding chronic ventilation are made and as an alternative means of ventilation for those who refuse tracheostomy. CONCLUSIONS: Non-invasive ventilation may be used in patients with profound muscle weakness, as a means of enhancing patient autonomy by improving communication and maintaining ventilation until decisions about ongoing care are made.

Air embolism--a case series and review.

Venous or arterial air embolism may be a life threatening event. The condition is seen in many fields of medicine, including intensive care. We present a series of three cases of air embolism encountered in the intensive care unit, which demonstrate different pathophysiologies for air embolism in critically ill patients. We also review the literature with respect to aetiology, incidence, pathophysiology, diagnosis and treatment options for venous and arterial embolism.

Percutaneous tracheostomy--long-term outlook, a review.

OBJECTIVE: To review the techniques and long term complications of the various techniques of percutaneous tracheostomy in the critically ill patient. DATA SOURCES: A review of studies reported on the various percutaneous tracheostomy techniques. SUMMARY OF REVIEW: A tracheostomy is frequently performed in the critically ill patient when prolonged mechanical ventilation, airway protection and pulmonary toilet are required. It is also facilitates weaning from mechanical ventilation, reduces laryngeal injury and improves patient comfort thus decreasing the need for sedation. The percutaneous dilatational technique can be easily and rapidly performed at the bedside. Short-term complication rates associated with percutaneous tracheostomies range between 7-22% and include bleeding, pneumothorax, subcutaneous emphysema, paratracheal insertion, posterior tracheal wall laceration, damage to or insertion through the endotracheal tube, hypoxia, hypotension and arrhythmias, cuff leak, endotracheal tube obstruction, loss of airway, premature extubation and wound infection. Peri-operative mortality ranges from 0.2 to 0.7%. The incidence of these complications often depends on the experience of the operator. Long-term complications and their incidence are not as well defined. CONCLUSIONS: In the critically ill patient who requires a tracheostomy, the percutaneous tracheostomy has become the method of choice as it can be performed at the bedside, leaves a smaller scar after decannulation and may be associated with fewer complications compared with the standard surgical technique.

Long-term outcomes following percutaneous tracheostomy using the Griggs technique.

Percutaneous tracheostomy is commonly performed in the intensive care unit. This study assesses the long-term outcomes following percutaneous tracheostomy using the Griggs technique. We carried out a prospective observational cohort study. Two hundred and eight patients who had undergone percutaneous tracheostomy between 1 September 1996 and 31 July 2000 and who were alive at least six months following the procedure, were included in the study. Median follow-up was at 30 months. All patients were sent questionnaires regarding relevant symptoms. One hundred and six (51%) responded and were invited for further follow-up. Forty-three (20.6%) patients underwent scar evaluation by the investigators and 41/208 (19.7%) underwent spirometry. Of the responders, 38% complained of some degree of voice change and 12% complained of ongoing severe cough. Thirty-one per cent complained of shortness of breath, with more than half of these having concomitant heart or lung disease, which may explain this. Eighty-one per cent of patients had minimally visible or a visible but neat scar. Eight patients (8/41 (19.5%)) had some evidence of upper airway obstruction on spirometry, but only 2/41 (5% of patients) were symptomatic (stridor or shortness of breath). We conclude that percutaneous tracheostomy using the Griggs technique has an acceptable long-term complication rate.

The effects of inhalation of a novel nitric oxide donor, DETA/NO, in a patient with severe hypoxaemia due to acute respiratory distress syndrome.

Aerosolized NONOates have been investigated in animal models in acute pulmonary hypertension, but none have been used in humans. We report the first use of aerosolized diethylenetriamine nitric oxide adduct (DETA/NO), a NONOate, in a patient with severe acute respiratory distress syndrome. Both pulmonary vascular resistance index and mean pulmonary arterial pressure were reduced by a mean of 26% and 18% respectively after the administration of a single dose of DETA/NO (150 micromol). Intrapulmonary shunting also improved. There were no significant changes in systemic arterial pressure or arterial methaemoglobin concentration after DETA/NO inhalation. We conclude that DETA/NO aerosol produced selective pulmonary vasodilation, with an improvement in pulmonary haemodynamics and oxygenation, while having no measurable effect on the systemic circulation.

Plasmapheresis for thrombotic thrombocytopenic purpura following bone marrow transplantation.

Recognition of thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS) following bone marrow transplantation (BMT) has increased in recent years. The use of plasma exchange has greatly improved the outlook of de novo TTP. Fewer data are available on its use in post-BMT TTP but small uncontrolled series showed poor results with low response rates. We present here a case of a young patient who developed manifestations of TTP 10 months after BMT with complete recovery following treatment with plasma exchange for 1 month. This case suggests that plasma exchange could be life saving and should be tried in every patient with post-BMT TTP.

Phenotypic-genotypic analysis of CYP2C19 in the Jewish Israeli population.

OBJECTIVES: Evaluation of CYP2C19 activity and the frequency of CYP2C19 alleles in the Jewish Israeli population. METHODS: One hundred forty Jewish Israeli subjects received 100 mg racemic mephenytoin and collected urine for 8 hours. Urinary concentrations of mephenytoin enantiomers and 4'-hydroxymephenytoin were determined by gas-liquid chromatography and HPLC, respectively. CYP2C19 activity was derived from urinary S/R-ratio and 8-hour urinary excretion of 4'-hydroxymephenytoin. Mutations were identified by polymerase chain reaction and enzyme digestion with SmaI (CYP2C19*2) and BamHI (CYP2C19*3). RESULTS: Deficient mephenytoin hydroxylation was found in 4 subjects (2.9%; 95% confidence interval [CI], 0.1% to 5.7%) who were homozygous for CYP2C19*2. CYP2C19*2 was the major deactivating allele accounting for 15% (95% CI, 11% to 19%) of CYP2C19 alleles, whereas CYP2C19*3 was identified in 2 subjects (1%; 95% CI, 0% to 2%). Among 136 extensive metabolizers, 99 were homozygous for CYP2C19*1 and 37 were compound heterozygous CYP2C19*1/CYP2C19*2 (35 subjects) or CYP2C19*1/CYP2C19*3 (2 subjects). Gene dose effect was noted so that the S/R-ratio was significantly greater and urinary excretion of 4'-hydroxymephenytoin was significantly lower in compound heterozygous than in homozygous extensive metabolizers (0.310+/-0.209 versus 0.225+/-0.176, P < .04 and 48.6%+/-19.2% versus 56.3%+/-16.0%, P < .03, respectively). Female extensive metabolizers had a significantly lower excretion of 4'-hydroxymephenytoin than male extensive metabolizers (49.5%+/-17.6% versus 58.4%+/-16.7%, respectively, P < .005). CONCLUSION: The frequency of poor metabolizers of CYP2C19 and CYP2C19*2 allele in the Jewish Israeli population resembles findings in non-Asian populations. Complete concordance was noted between phenotypic and genotypic findings. CYP2C19 genotyping may enable subclassification of extensive metabolizers into subjects with high and low activity.

Ticlopidine-induced thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) occurs in association with a wide variety of disorders including infections, connective tissue diseases, and solid organ tumors. It also may coincide with administration of drugs such as mitomycin, metronidazole, oral contraceptives, cyclosporine, and many others. We report the occurrence of TTP in a patient shortly after the initiation of ticlopidine.

Second degree atrio-ventricular block and cardiotoxicity secondary to envenomation by the scorpion Leiurus quinquestriatus ('yellow scorpion')--an indication for serotherapy?

Tachyarrhythmia following scorpion envenomation might be an indication for anti venin therapy. We present a case of an unusual cardiotoxic response to Leiurus quinquestriatus ('yellow scorpion') venom-second degree atrio-ventricular block (Mobitz type 1). We review the biological activities of L. quinquestriatus' venom and the arrhythmia's possible pathophysiology. The question arising from this case is the therapeutic approach to cardiotoxicity and bradyarrhythmias induced by scorpion envenomation-mainly, the indication for anti serum therapy.