Major sources of critical incidents in intensive care.

INTRODUCTION: In recent years, critical incident (CI) reporting has increasingly been regarded as part of ongoing quality management. CI databanks also aim to improve health and safety issues for patients as well as staff. The aim of this study was to identify frequent causes of adverse events in critical care with the potential to harm patients, staff or visitors by analysing data from a voluntary and optionally anonymous critical incident reporting system. METHODS: The study includes all critical incidents reported during a 90-month period in a 13-bed adult general intensive care unit (ICU). Reporting of incidents was performed via an electronic reporting system or by a manual critical incident report. All CIs were classified in the following main categories: equipment, administration, pharmaceuticals, clinical practice, and health & safety hazards. The overall distribution of incidents within the different categories was compared with the regional database of ICUs in the Cheshire and Mersey region of northwest England for 2008. RESULTS: A total of 1127 CIs were reported during the study period. The frequencies within the main categories were: equipment 338 (30%), clinical practice 257 (22.8%), pharmaceuticals 238 (21.1%), administration 213 (18.9%), health and safety hazards 81 (7.2%). The regional database had a similar frequency of critical incidents within the different categories, suggesting that our results may reflect a general distribution pattern of CIs in intensive care. CONCLUSIONS: Critical incident reporting helps to identify frequent causes of adverse events in critical care. Improvements in quality of care following implementation of preventative strategies such as introduction of regular equipment training sessions will have to be assessed further in future studies.

Adenovirus Type 7 causing severe lower respiratory tract infection in immunocompetent adults: a comparison of two contrasting cases from an intensive care unit in North West England.

OBJECTIVES: Severe lower respiratory tract infection caused by adenovirus is well described in immunocompromised hosts and can cause significant morbidity and mortality. We compare and contrast the clinical presentation, radiological, and virological features of two rare cases in immunocompetent adults admitted to an intensive care unit in a large, teaching hospital in North West England. We then provide a concise, comprehensive literature review. METHODS: The first case was a 35-year old female asthmatic who presented with respiratory distress and pneumonitis during peak influenza season, and recovered after a prolonged hospital stay. The second case was a 73-year old male who presented with diarrhoea, vomiting, and general malaise outside of influenza season, developed respiratory compromise, and died. Adenovirus type 7 was identified in bronchoalveolar lavages and plasma samples of both patients, each of whom received cidofovir. No other infectious aetiology was identified. RESULTS: Clinical and radiological features of severe lower respiratory tract adenoviral infection are similar to other infectious causes of pneumonia and ARDS, including severe influenza. This can create diagnostic uncertainty, especially during influenza season. Positive adenovirus polymerase chain reaction results can support a diagnosis of severe lower respiratory tract adenovirus infection in patients with a clinically compatible syndrome and no other identified aetiology, with higher viral loads being associated with worse prognosis. Although treatment is predominantly supportive, early use of cidofovir may improve outcomes. CONCLUSIONS: These rare cases highlight that severe lower respiratory tract adenoviral infection should be considered in the differential diagnoses of immunocompetent patients presenting with pneumonia and ARDS.

Surface electrostimulation of acupuncture points for sedation of critically ill patients in the intensive care unit--a pilot study.

BACKGROUND: This is a pilot study to investigate the effects of electrostimulation of acupuncture points on sedation and the dose of sedatives in the Intensive Care Unit. METHODS: Electrostimulation of acupuncture points was performed on 12 critically ill patients requiring sedation for mechanical ventilation. Electrostimulation was applied by point surface electrodes at LI4, ST36, HT7 and LR3 points for 20 minutes every hour for 12 hours using dense dispersed mode with a current frequency of 10-100 Hz and maximum intensity of 10 mA. All patients were sedated with propofol and alfentanil as required. The dose of propofol was reduced by 10mg/hour provided the patient remained sedated according to our guidelines. Sedation and analgesia scores, dose of sedative and analgesics drugs, respiratory rate, heart rate, mean arterial blood pressure and compliance with the ventilator were recorded before electrostimulation of acupuncture points, and hourly thereafter for 12 hours. RESULTS: There was significant reduction in the median propofol consumption from 145 mg/hour (range 30-250) to 15 mg/hour (range 0-250) (P<0.05), without any significant change in sedation scores or analgesia scores. The haemodynamic and respiratory variables remained stable. All patients were compliant with the ventilator. CONCLUSIONS: This pilot study showed significant reduction in the dose of propofol required for sedation in critically ill patients following surface electrostimulation of acupuncture points, without any adverse effects. A randomised controlled trial is warranted.

Preventing constipation in critically ill patients.

In 2003 an audit was carried out on an ICU which demonstrated that the incidence of constipation was high and that this could contribute to the failure to wean patients from mechanical ventilation (Mostafa et al, 2003). A protocol was introduced to standardise the assessment and management of constipation. This article explores why patients in intensive care are at risk of constipation and presents the results of a second audit, carried out after the protocol was introduced, to assess its impact on patients.

Effect of selenium supplementation on biochemical markers and outcome in critically ill patients.

BACKGROUND & AIMS: This study aimed to assess the effect of high dose selenium (Se) supplementation on Se status in blood, oxidative stress, thyroid function and possible effects on requirement for renal replacement therapy (RRT) in severely septic patients admitted to the intensive care unit (ICU). METHODS: This prospective single-centre study was carried out in 40 septic ICU patients who were randomized to high dose Se (Se+ group, N=18 (474, 316, 158 microg/day), each for 3 consecutive days followed by a standard dose of 31.6 microg/day of Se given as sodium selenite whereas the control group (Se-, N=22) received only the standard dose of Se. Plasma Se, glutathione peroxidase (GSH-Px), F2 isoprostanes, thyroid function tests (total T4 and total T3), C-reactive protein (CRP) and red blood cell (RBC) GSH-Px were estimated on day 0, 3, 7, 14. RESULTS: In the Se+ group, plasma Se increased by day 3 and 7 (P<0.0001) and day 14 (P=0.02), plasma GSH-Px increased by day 3 and 7 (P=0.01) as compared to Se- group. There was a significant negative correlation between plasma Se and SOFA (sepsis related organ failure assessment) (r=-0.36, P=0.03) along with low plasma Se and high CRP at the time of admission. Requirement for renal replacement therapy was not significantly different between the groups. CONCLUSION: Although high dose Se supplementation increased plasma Se and GSH-Px activity, it did not reduce oxidative damage or the requirement for RRT. Se levels in blood are influenced by redistribution and severity of illness and therefore should be interpreted with caution.

Markers of oxidative damage, antioxidant status and clinical outcome in critically ill patients.

BACKGROUND: Oxidative stress is a consequence of critical illness, and may have an impact on survival. We studied markers of oxidative damage and antioxidant (AO) protection and compared them with clinical scores and outcome. METHODS: Blood sampling and clinical scoring was carried out on 60 consecutively admitted intensive therapy unit (ITU) patients within 24 h of admission and then every three days of ITU stay. The patients included 30 surgical and 30 medical patients, of whom 46 survived their stay in ITU. Clinical scoring was by Acute Physiology and Chronic Health Evaluation (APACHE) II score, multiple organ dysfunction (MOD) score and sepsis rating. Oxidative damage was assessed by measurement of plasma malondialdehyde (MDA) and F2 isoprostanes (F2 IsoPs). AO protection was assessed by measurement of plasma total AO status, AO gap, ascorbic acid and the enzymes glutathione peroxidase and superoxide dismutase. RESULTS: Both clinical markers, APACHE II and MOD, and oxidative damage markers MDA and F2 IsoPs were significantly higher in non-survivors (NS) than in survivors (S) at the time of admission. Median (interquartile ranges) were (APACHE II), 14[12--17] (S), 20.5[16.7--22.2] (NS),P<0.0001; (MOD), 3.0[2.0--5.0] (S), 8.0[4.7--9.2] (NS), P<0.0005; (MDA, mumol/L), 0.22[0.19--0.27] (S), 0.25[0.20--0.34] (NS), P=0.04 and (F2 IsoPs, pg/mL), 9.7[6.0--9.9] (S), 11.0[9.0--12.0] (NS), P=0.01. Oxidative damage markers reduced (improved) in the survivors but increased in the non-survivors. There was little difference between the groups in AO protection markers. There was a significant positive correlation between MOD and markers of oxidative damage at the time of admission (r=0.40, P=0.003, F2 IsoPs; r=0.28, P=0.035, MDA) and between the oxidative damage markers themselves (r=0.32, P=0.017). CONCLUSION: Increased oxidative stress is associated with poor outcome in critically ill patients, and may be a prognostic indicator. Oxidative damage markers are more useful than AO protection markers in predicting outcome.

Lipoprotein-complexed C-reactive protein and the biphasic transmittance waveform in critically ill patients.

The 'biphasic transmittance waveform' (BTW) refers to a decrease in light transmittance that often occurs prior to clotting in coagulation assays of critically ill patient plasmas. It correlates with disseminated intravascular coagulation and mortality. The present work shows that the BTW is due to the rapid formation of a precipitate and a coincident change in turbidity in re-calcified plasma. The precipitate was isolated from patient plasma and contained lipids typical of very low density lipoprotein (VLDL), plus the proteins apolipoprotein B-100 and C-reactive protein (CRP). Precipitation also occurred in normal plasma supplemented with CRP. In addition, CRP precipitated with VLDL and intermediate density lipoprotein, but not low density lipoprotein or high density lipoprotein. The Kd value for the CRP/VLDL interaction is 340 nM. The IC50 value of Ca2+ for complex formation is 5.0 mM, and epsilon-aminocaproic acid inhibits the process. In 15 plasmas with the BTW from critically ill patients, CRP was highly elevated (77-398 microg/mL) and VLDL cholesterol ranged from 0.082 to 1.32 mM. The magnitude of the turbidity change on re-calcification correlated well with the calculated level of the CRP/VLDL complex. Thus, the Ca2+-dependent formation of a complex between CRP and VLDL accounts for the BTW.

Low plasma granulocyte-macrophage colony stimulating factor is an indicator of poor prognosis in sepsis.

OBJECTIVE: Monocyte dysfunction has been shown to be associated with adverse consequences in septic patients. The cytokine growth factor granulocyte-macrophage colony stimulating factor (GM-CSF) may be required for optimal monocyte function in these patients. The current study investigates whether plasma GM-CSF levels were significantly different in septic patients and whether there was an association with prognosis. DESIGN: Plasma samples were collected from all septic patients from day 1 of the diagnosis of sepsis for 3 days. Healthy volunteer plasma served as control samples. A novel enzyme-linked immuno-adsorbent assay was developed with suitable sensitivity for detection of GM-CSF in patient and normal plasma. APACHE II score, age, sex and outcome were determined for all patients. SETTING: A single centre study at the Royal Liverpool University Hospital in a medico-surgical 13 bed intensive care unit. PATIENTS: All septic patients (n = 53) fulfilling the criteria of the APCC for the diagnosis of sepsis, were recruited for the study with informed consent from day 1 of the diagnosis of sepsis and plasma GM-CSF measured on three consecutive days. Patients were excluded from the study if on immunosuppressive therapy. Normal healthy volunteers (n = 33) were included in the study to serve as controls. RESULTS: Plasma GM-CSF levels were statistically significantly depressed in patients who died compared with those who survived, who had levels comparable with healthy controls. CONCLUSIONS: The results indicate that low plasma GM-CSF is associated with adverse consequences for septic patients. The measurement of GM-CSF in the plasma of septic patients merits further study for use as a prognostic marker and also to identify the type of immunotherapy the patient may benefit from.

Is low monocyte HLA-DR expression helpful to predict outcome in severe sepsis?

OBJECTIVE: Low monocyte human leukocyte antigen-DR (HLA-DR) expression has been reported to be an indicator of poor survival in critically ill septic patients. We assessed its usefulness as a prognostic indicator in order to identify possible interventions to normalise HLA-DR expression in those patients with lowered monocyte HLA-DR. DESIGN: HLA-DR expression was measured on separated monocytes of septic patients, using flow cytometry, and HLA-DR upregulation was measured by the same techniques after ex vivo stimulation with granulocyte macrophage colony stimulating factor (GM-CSF). APACHE II score, age, sex and outcome were determined for all patients. SETTING: A single-centre study at the Royal Liverpool University Hospital in a medico-surgical 13-bed intensive care unit. PATIENTS AND PARTICIPANTS: All septic patients ( n=70) fulfilling the criteria of the ACCP for the diagnosis of sepsis were recruited for the study with informed consent from day 1 of diagnosis of sepsis and monocyte HLA-DR expression measured on 3 consecutive days. Patients were excluded from the study if they were on immunosuppressive therapy. Normal healthy volunteers ( n=45) were included. RESULTS: Low monocyte surface expression and median fluorescence density HLA-DR expression was not associated with a high mortality. High APACHE II scores were not correlated with low HLA-DR expression. However, in those patients where HLA-DR expression was lowered, this could be restored ex vivo by GM-CSF. CONCLUSIONS: In the group of septic patients under study, HLA-DR was not a useful prognostic marker of outcome. We did not find a higher mortality in the group of patients who had low expression. These findings are contradictory to some previously reported findings, and the possible reasons are discussed.

Early identification of sepsis and mortality risks through simple, rapid clot-waveform analysis. Implications of lipoprotein-complexed C reactive protein formation.

OBJECTIVE: To determine if the rapid waveform profile of the activated partial thromboplastin time (aPTT) assay, which detects lipoprotein-complexed C reactive protein (LCCRP) formation, predicts sepsis and mortality in critically ill patients. DESIGN: Observational, cohort study. SETTING: General intensive therapy unit (ITU) of a tertiary care hospital. PATIENTS AND PARTICIPANTS: A total of 1187 consecutive patients admitted to the ITU. INTERVENTION: Activated partial thromboplastin time transmittance waveform analysis was performed within the first hour of admission to the ITU. The degree of change causing a biphasic waveform was quantified through the drop in light transmittance level. MEASUREMENTS AND RESULTS: Three hundred forty-six patients had a biphasic waveform on admission to the ITU with a mortality rate of 44% compared with 26% for those with normal waveforms. Logistic regression models showed direct correlation between the likelihood for sepsis and in-patient mortality with increasing waveform abnormalities. The mortality fraction was 0.3 with normal waveforms versus 0.6 when the light transmittance decreased by 30%. The odds ratio (OR) for mortality and sepsis were 4.5 and 11, respectively, from the most abnormal to normal aPTT waveforms. These were comparable with APACHE II scores and superior to those estimated by CRP for mortality (OR 2.3) / sepsis (OR 6.4) prediction. CONCLUSION: Waveform analysis within the first hour of ITU admission is a single, simple and rapid method of identifying the risks of mortality and sepsis. Its measure of LCCRP formation shows superior prediction over CRP alone and it warrants further assessment as a tool to triage and target prompt, appropriate treatment in the ITU.

HLA-DR regulation and the influence of GM-CSF on transcription, surface expression and shedding.

Low surface HLA-DR expression is a feature in sepsis. However, the mechanisms that regulate HLA-DR expression have not been elucidated. The current study investigates regulation of HLA-DR gene transcription, post transcriptional events and shedding of surface HLA-DR, as well as the regulation of HLA-DR by GM-CSF and an immunomodulatory cytokine. Plasma and PBMC were collected from septic patients and healthy volunteers. An ELISA was developed to measure soluble HLA. PCR techniques were used to determine HLA-DR mRNA levels, and flow cytometry and fluorescent microscopy were used for measurement of surface expressed and intracellular HLA-DR. Septic patients fulfilling the criteria of the American College of Chest Physicians (ACCP) for sepsis were recruited for the study (n=70). HLA-DR was measured on three consecutive days, days seven and fourteen. Patients were excluded from the study if on immunosuppressive therapy. Results: Higher levels of shed HLA-DR were found in the plasma of septic patients compared to healthy controls. The level of HLA-DR mRNA was significantly lower in septic patients compared to healthy controls, however an increased intracellular HLA-DR expression was observed. When HL-60 cells were treated with GM-CSF, gene transcription, surface expression and shedding of HLA-DR were all up-regulated. These results indicate that the mechanisms involved in the regulation of HLA-DR in sepsis include shedding of HLA-DR from the cell surface and regulation of HLA-DR gene transcription. Post-translational processing of HLA-DR was also seen to be compromised. GM-CSF was shown to regulate HLA-DR at all these levels.

Biphasic transmittance waveform in the APTT coagulation assay is due to the formation of a Ca(++)-dependent complex of C-reactive protein with very-low-density lipoprotein and is a novel marker of impending disseminated intravascular coagulation.

A decrease in light transmittance before clot formation, manifesting as a biphasic waveform (BPW) pattern in coagulation assays, was previously correlated with the onset of disseminated intravascular coagulation (DIC). In this study of 1187 consecutive admissions to the intensive care unit, the degree of this change on admission predicts DIC better than D-dimer measurements. Additionally, the BPW preceded the time of DIC diagnosis by 18 hours, on average, in 56% (203 of 362) of DIC patients. The BPW is due to the rapid formation of a precipitate and coincident turbidity change on recalcification of plasma. The isolated precipitate contains very-low-density lipoprotein (VLDL) and C-reactive protein (CRP). The addition of CRP and Ca(++) to normal plasma also causes the precipitation of VLDL and IDL, but not LDL or HDL. The K(d) of the CRP/VLDL interaction is 340 nM, and the IC(50) for Ca(++) is 5.0 mM. In 15 plasmas with the BPW, CRP was highly elevated (77-398 microg/mL), and the concentration of isolated VLDL ranged from 0.082 to 1.32 mM (cholesterol). The turbidity change on recalcification correlates well with the calculated level of the CRP-VLDL complex. Clinically, the BPW better predicts for DIC than either CRP or triglyceride alone. The complex may have pathophysiological implications because CRP can be detected in the VLDL fraction from sera of patients with the BPW, and the VLDL fraction has enhanced prothrombinase surface activity. The complex has been designated lipoprotein complexed C-reactive protein.