Geoff Bellingan

Medication errors: a prospective cohort study of hand-written and computerised physician order entry in the intensive care unit

IntroductionThe study aimed to compare the impact of computerised physician order entry (CPOE) without decision support with hand-written prescribing (HWP) on the frequency, type and outcome of medication errors (MEs) in the intensive care unit.MethodsDetails of MEs were collected before, and at several time points after, the change from HWP to CPOE. The study was conducted in a London teaching hospitals 22-bedded general ICU. The sampling periods were 28 weeks before and 2, 10, 25 and 37 weeks after introduction of CPOE. The unit pharmacist prospectively recorded details of MEs and the total number of drugs prescribed daily during the data collection periods, during the course of his normal chart review.ResultsThe total proportion of MEs was significantly lower with CPOE (117 errors from 2429 prescriptions, 4.8%) than with HWP (69 errors from 1036 prescriptions, 6.7%) (p < 0.04). The proportion of errors reduced with time following the introduction of CPOE (p < 0.001). Two errors with CPOE led to patient harm requiring an increase in length of stay and, if administered, three prescriptions with CPOE could potentially have led to permanent harm or death. Differences in the types of error between systems were noted. There was a reduction in major/moderate patient outcomes with CPOE when non-intercepted and intercepted errors were combined (p = 0.01). The mean baseline APACHE II score did not differ significantly between the HWP and the CPOE periods (19.4 versus 20.0, respectively, p = 0.71).ConclusionIntroduction of CPOE was associated with a reduction in the proportion of MEs and an improvement in the overall patient outcome score (if intercepted errors were included). Moderate and major errors, however, remain a significant concern with CPOE.

Trial of the Route of Early Nutritional Support in Critically Ill Adults

BACKGROUND Uncertainty exists about the most effective route for delivery of early nutritional support in critically ill adults. We hypothesized that delivery through the parenteral route is superior to that through the enteral route. METHODS We conducted a pragmatic, randomized trial involving adults with an unplanned admission to one of 33 English intensive care units. We randomly assigned patients who could be fed through either the parenteral or the enteral route to a delivery route, with nutritional support initiated within 36 hours after admission and continued for up to 5 days. The primary outcome was all-cause mortality at 30 days. RESULTS We enrolled 2400 patients; 2388 (99.5%) were included in the analysis (1191 in the parenteral group and 1197 in the enteral group). By 30 days, 393 of 1188 patients (33.1%) in the parenteral group and 409 of 1195 patients (34.2%) in the enteral group had died (relative risk in parenteral group, 0.97; 95% confidence interval, 0.86 to 1.08; P=0.57). There were significant reductions in the parenteral group, as compared with the enteral group, in rates of hypoglycemia (44 patients [3.7%] vs. 74 patients [6.2%]; P=0.006) and vomiting (100 patients [8.4%] vs. 194 patients [16.2%]; P<0.001). There were no significant differences between the parenteral group and the enteral group in the mean number of treated infectious complications (0.22 vs. 0.21; P=0.72), 90-day mortality (442 of 1184 patients [37.3%] vs. 464 of 1188 patients [39.1%], P=0.40), in rates of 14 other secondary outcomes, or in rates of adverse events. Caloric intake was similar in the two groups, with the target intake not achieved in most patients. CONCLUSIONS We found no significant difference in 30-day mortality associated with the route of delivery of early nutritional support in critically ill adults. (Funded by the United Kingdom National Institute for Health Research; CALORIES Current Controlled Trials number, ISRCTN17386141.).

Hematopoietic prostaglandin D2 synthase controls the onset and resolution of acute inflammation through PGD2 and 15-deoxyΔ12–14 PGJ2

Hematopoietic prostaglandin D2 synthase (hPGD2S) metabolizes cyclooxygenase (COX)-derived PGH2 to PGD2 and 15-deoxyΔ12–14 PGJ2 (15d-PGJ2). Unlike COX, the role of hPGD2S in host defense is ambiguous. PGD2 can be either pro- or antiinflammatory depending on disease etiology, whereas the existence of 15d-PGJ2 and its relevance to pathophysiology remain controversial. Herein, studies on hPGD2S KO mice reveal that 15d-PGJ2 is synthesized in a self-resolving peritonitis, detected by using liquid chromatography–tandem MS. Together with PGD2 working on its DP1 receptor, 15d-PGJ2 controls the balance of pro- vs. antiinflammatory cytokines that regulate leukocyte influx and monocyte-derived macrophage efflux from the inflamed peritoneal cavity to draining lymph nodes leading to resolution. Specifically, inflammation in hPGD2S KOs is more severe during the onset phase arising from a substantial cytokine imbalance resulting in enhanced polymorphonuclear leukocyte and monocyte trafficking. Moreover, resolution is impaired, characterized by macrophage and surprisingly lymphocyte accumulation. Data from this work place hPGD2S at the center of controlling the onset and the resolution of acute inflammation where it acts as a crucial checkpoint controller of cytokine/chemokine synthesis as well as leukocyte influx and efflux. Here, we provide definitive proof that 15d-PGJ2 is synthesized during mammalian inflammatory responses, and we highlight DP1 receptor activation as a potential antiinflammatory strategy.

Community-acquired pneumonia on the intensive care unit: secondary analysis of 17,869 cases in the ICNARC Case Mix Programme Database

IntroductionThis paper describes the case mix, outcome and activity for admissions to intensive care units (ICUs) with community-acquired pneumonia (CAP).MethodsWe conducted a secondary analysis of a high quality clinical database, the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme Database, of 301,871 admissions to 172 adult ICUs across England, Wales and Northern Ireland, 1995 to 2004. Cases of CAP were identified from pneumonia admissions excluding nosocomial pneumonias and the immuno-compromised. It was not possible to review data from the time of hospital admission; therefore, some patients who developed hospital-acquired/nosocomial pneumonia may have been included.ResultsWe identified 17,869 cases of CAP (5.9% of all ICU admissions). There was a 128% increase in admissions for CAP from 12.8 per unit to 29.2 per unit during the study period compared to only a 24% rise in total ICU admissions (p < 0.001). Eighty-five percent of admissions were from within the same hospital. Fifty-nine percent of cases were admitted to the ICU <2 days, 21.5% between 2 and 7 days, and 19.5% >7 days after hospital admission. Between 1995 and 1999 and 2000 and 2004 there was a rise in admissions from accident and emergency (14.8% to 16.8%; p < 0.001) and high dependency units (6.9% to 11.9%; p < 0.001) within the same hospital, those aged >74 (18.5 to 26.1%; p < 0.001), and mean APACHE II score (6.83 to 6.91; p < 0.001). There was a fall in past history of severe respiratory problems (8.7% to 6.4%; p < 0.001), renal replacement therapy (1.6% to 1.2%; p < 0.01), steroid treatment (3.4% to 2.8%; p < 0.05), sedation/paralysis (50.2% to 40.4%; p < 0.001), cardiopulmonary resuscitation prior to admission (7.5% to 5.5%; p < 0.001), and septic shock (7.3% to 6.6%; p < 0.001). ICU mortality was 34.9% and ultimate hospital mortality 49.4%. Mortality was 46.3% in those admitted to the ICU within 2 days of hospital admission rising to 50.4% in those admitted at 2 to 7 days and 57.6% in those admitted after 7 days following hospital admission.ConclusionCAP makes up a small, but important and rising, proportion of adult ICU admissions. Survival of over half of all cases vindicates the use of ICU facilities in CAP management. Nevertheless, overall mortality remains high, especially in those admitted later in their hospital stay.

TREM‐1 promotes survival during septic shock in mice

Triggering receptor expressed on myeloid (TREM)‐1 is integral to the inflammatory response occurring during septic shock, although its precise function has yet to be determined. Here we show that in vivo silencing of TREM‐1 using siRNA duplexes in a fecal peritonitis mouse model resulted in a blunted inflammatory response and increased mortality. This was associated with impaired bacterial clearance related to marked inhibition of the neutrophil oxidative burst. By contrast, TREM‐1‐silenced mice were highly resistant to a lethal endotoxin challenge, while partial silencing of TREM‐1 in the bacterial peritonitis model produced a significant survival benefit. These data highlight the crucial role of the TREM‐1 pathway in mounting an adequate inflammatory and cytotoxic response to polymicrobial sepsis, and both the therapeutic promise and potential risks of its modulation.

Door-opening motion can potentially lead to a transient breakdown in negative-pressure isolation conditions: the importance of vorticity and buoyancy airflows

Summary A patient with severe chickenpox was admitted to a negative-pressure isolation room. He remained sedated, intubated and mechanically ventilated throughout his admission. He was managed only by nurses immune to chickenpox. A non-immune male nurse occasionally handed equipment through the doorway, without entering the room. Ten days later, he also developed chickenpox. Sequencing of viruses from the patient and nurse showed the same rare genotype, indicating nosocomial transmission. An experimental model demonstrated that, despite negative pressure, opening the door could have resulted in transport of infectious air out of the isolation room, leading to a breakdown in isolation conditions.

Novel biphasic role for lymphocytes revealed during resolving inflammation

Acute inflammation is traditionally described as the influx of polymorphonuclear leukocytes (PMNs) followed by monocyte-derived macrophages, leading to resolution. This is a classic view, and despite subpopulations of lymphocytes possessing innate immune-regulatory properties, seldom is their role in acute inflammation and its resolution discussed. To redress this we show, using lymphocyte-deficient RAG1−/− mice, that peritoneal T/B lymphocytes control PMN trafficking by regulating cytokine synthesis. Once inflammation ensues in normal mice, lymphocytes disappear in response to DP1 receptor activation by prostaglandin D2. However, upon resolution, lymphocytes repopulate the cavity comprising B1, natural killer (NK), γ/δ T, CD4+/CD25+, and B2 cells. Repopulating lymphocytes are dispensable for resolution, as inflammation in RAG1−/− and wild-type mice resolve uniformly. However, repopulating lymphocytes are critical for modulating responses to superinfection. Thus, in chronic granulomatous disease using gp91phox−/− mice, not only is resolution delayed compared with wild-type, but there is a failure of lymphocyte re-appearance predisposing to exaggerated immune responses upon secondary challenge that is rescued by resolution-phase lymphocytes. In conclusion, as lymphocyte repopulation is also evident in human peritonitis, we hereby describe a transition in T/B cells from acute inflammation to resolution, with a central role in modulating the severity of early onset and orchestrating responses to secondary infection.

Dissemination of intraperitoneal ovarian cancer: Discussion of mechanisms and demonstration of lymphatic spreading in ovarian cancer model

Ovarian cancer is often accompanied by severe ascites. This complication aggravates the disease per se and the chances for its successful treatment. The etiology of ascites is not well understood nor are efficient therapies for ascites available. These empirical observations support the view that ascites might be caused by blocking of lymphatic vessels. Furthermore, it suggests that cancer cells might be the blocking agent and could use lymphatic vessels for metastatic spreading. To test this hypothesis, we used labeled cancer cells in an immuno-competent animal model of ovarian cancer and followed their dissemination. These NuTu-19 cells are ovarian cancer cells derived from normal rat ovarian epithelial cells, the origin of the most frequent ovarian cancer. Thus studying NuTu-19 cell behavior in an animal model is likely to reflect the progression of the human disease. To unambiguously document the migration of NuTu-19 cells from the peritoneum to remote organs, we generated EGFP expressing NuTu-19 cells by transduction with EGFP-lentiviral vectors. The EGFP positive NuTu-19 cells were injected intraperitoneally into immuno-competent FISHER 344 rats, and the metastatic spreading was monitored. Metastases were observed on the peritoneum, the omentum and in the parathymus. This clearly demonstrates that systemic spreading of NuTu-19 ovarian cancer cells is conducted by lymphatic ways. Animals die 7 weeks after injection, with severe ascites, which suggests that blockage of lymphatic drainage by the cancer cell growth is an important complication of the disease.

Large variation in MRSA policies, procedures and prevalence in English intensive care units: a questionnaire analysis

ObjectiveMethicillin-resistant Staphylococcus aureus (MRSA) is a major problem in intensive care units in most countries. Despite recommendations for screening and isolation of patients with MRSA our perception has been that there is little uniformity in approach in ICUs besides adherence to basic infection control procedures. We thus sought to identify MRSA prevalence and the variation of infection control policy across intensive care units in England.Design and settingPostal questionnaire with telephone follow-up in English intensive care units.Measurements and resultsResponses were obtained from 217 (96%) ICUs. Marked variation in practice was noted in terms of patient screening, staff screening, infection control procedures, isolation or cohorting of colonised/infected patients, and ward discharge policy. Point prevalence data showed that 16.2% of ICU patients were known to be colonised or infected with MRSA. There was a regional bias, but no difference was noted between high and low prevalence regions in terms of unit demographics or infection control policies.ConclusionsThis study highlights the lack of consistent policy across English ICUs regarding isolation, screening and discharge practices for MRSA. Prospective studies are urgently needed to determine best practice.

Utility of spa typing for investigating the local epidemiology of MRSA on a UK intensive care ward.

In the UK, meticillin-resistant Staphylococcus aureus (MRSA) is frequently endemic on intensive care units (ICUs), yet our understanding of the local epidemiology of MRSA within the ICU is poor and the best methods for preventing MRSA acquisition remain controversial. Newer molecular typing methods may aid epidemiological investigation of local MRSA strains. We applied Staphylococcal Protein A (spa) typing to MRSA strains collected from patients in a UK ICU. spa typing allowed better discrimination than multilocus sequence typing (MLST) but 73% of strains were either spa type t032 or t018 (associated with the prevalent UK MRSA strains, EMRSA-15 and EMRSA-16). MRSA infections were preceded by MRSA colonisation in 72% of patients, and in 88% of these, both commensal and disease-causing strains had identical MLST and spa types. spa typing helped elucidate the transmission of MRSA between patients for 19 strains with unusual spa types, although the high incidence of EMRSA-15 and -16 types t032 and t018 prevented its use for the majority of strains. Surprisingly, only four (9%) of 45 new MRSA isolates occurring within 28 days of isolation of an unusual spa type could have been due to cross-contamination. These results suggest that prompt transmission of MRSA between patients is rare in our ICU, at least for those strains with unusual spa types.