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1.  Pulmonary embolism in intensive care unit: Predictive factors, clinical manifestations and outcome 
Annals of Thoracic Medicine  2010;5(2):97-103.
OBJECTIVE:
To determine predictive factors, clinical and demographics characteristics of patients with pulmonary embolism (PE) in ICU, and to identify factors associated with poor outcome in the hospital and in the ICU.
METHODS:
During a four-year prospective study, a medical committee of six ICU physicians prospectively examined all available data for each patient in order to classify patients according to the level of clinical suspicion of pulmonary thromboembolism. During the study periods, all patients admitted to our ICU were classified into four groups. The first group includes all patients with confirmed PE; the second group includes some patients without clinical manifestations of PE; the third group includes patients with suspected and not confirmed PE and the fourth group includes all patients with only deep vein thromboses (DVTs) without suspicion of PE. The diagnosis of PE was confirmed either by a high-probability ventilation/perfusion (V/Q) scan or by a spiral computed tomography (CT) scan showing one or more filling defects in the pulmonary artery or in its branches. The diagnosis was also confirmed by echocardiography when a thrombus in the pulmonary artery was observed.
RESULTS:
During the study periods, 4408 patients were admitted in our ICU. The diagnosis of PE was confirmed in 87 patients (1.9%). The mean delay of development of PE was 7.8 ± 9.5 days. On the day of PE diagnosis, clinical examination showed that 50 patients (57.5%) were hypotensive, 63 (72.4%) have SIRS, 15 (17.2%) have clinical manifestations of DVT and 71 (81.6%) have respiratory distress requiring mechanical ventilation. In our study, intravenous unfractionated heparin was used in 81 cases (93.1%) and low molecular weight heparins were used in 4 cases (4.6%). The mean ICU stay was 20.2 ± 25.3 days and the mean hospital stay was 25.5 ± 25 days. The mortality rate in ICU was 47.1% and the in-hospital mortality rate was 52.9%. Multivariate analysis showed that factors associated with a poor prognosis in ICU are the use of norepinephrine and epinephrine. Furthermore, factors associated with in-hospital poor outcome in multivariate analysis were a number of organ failure associated with PE ≥ 3.
Moreover, comparison between patients with and without pe showed that predictive factors of pe are: acute medical illness, the presence of meningeal hemorrhage, the presence of spine fracture, hypoxemia with PaO2/FiO2 ratio <300 and the absence of pharmacological prevention of venous thromboembolism.
CONCLUSION:
Despite the high frequency of DVT in critically ill patients, symptomatic PE remains not frequently observed, because systematic screening is not performed. Pulmonary embolism is associated with a high ICU and in-hospital mortality rate. Predictive factors of PE are acute medical illness, the presence of meningeal hemorrhage, the presence of spine fracture, hypoxemia with PaO2/FiO2 < 300 and the absence of pharmacological prevention of venous thromboembolism.
doi:10.4103/1817-1737.62473
PMCID: PMC2883205  PMID: 20582175
ICU; predictive factors; prophylactic anticoagulation; pulmonary embolism
2.  An Economic Evaluation of Venous Thromboembolism Prophylaxis Strategies in Critically Ill Trauma Patients at Risk of Bleeding 
PLoS Medicine  2009;6(6):e1000098.
Using decision analysis, Henry Stelfox and colleagues estimate the cost-effectiveness of three venous thromboembolism prophylaxis strategies in patients with severe traumatic injuries who were also at risk for bleeding complications.
Background
Critically ill trauma patients with severe injuries are at high risk for venous thromboembolism (VTE) and bleeding simultaneously. Currently, the optimal VTE prophylaxis strategy is unknown for trauma patients with a contraindication to pharmacological prophylaxis because of a risk of bleeding.
Methods and Findings
Using decision analysis, we estimated the cost effectiveness of three VTE prophylaxis strategies—pneumatic compression devices (PCDs) and expectant management alone, serial Doppler ultrasound (SDU) screening, and prophylactic insertion of a vena cava filter (VCF)—in trauma patients admitted to an intensive care unit (ICU) with severe injuries who were believed to have a contraindication to pharmacological prophylaxis for up to two weeks because of a risk of major bleeding. Data on the probability of deep vein thrombosis (DVT) and pulmonary embolism (PE), and on the effectiveness of the prophylactic strategies, were taken from observational and randomized controlled studies. The probabilities of in-hospital death, ICU and hospital discharge rates, and resource use were taken from a population-based cohort of trauma patients with severe injuries (injury severity scores >12) admitted to the ICU of a regional trauma centre. The incidence of DVT at 12 weeks was similar for the PCD (14.9%) and SDU (15.0%) strategies, but higher for the VCF (25.7%) strategy. Conversely, the incidence of PE at 12 weeks was highest in the PCD strategy (2.9%), followed by the SDU (1.5%) and VCF (0.3%) strategies. Expected mortality and quality-adjusted life years were nearly identical for all three management strategies. Expected health care costs at 12 weeks were Can$55,831 for the PCD strategy, Can$55,334 for the SDU screening strategy, and Can$57,377 for the VCF strategy, with similar trends noted over a lifetime analysis.
Conclusions
The attributable mortality due to PE in trauma patients with severe injuries is low relative to other causes of mortality. Prophylactic placement of VCF in patients at high risk of VTE who cannot receive pharmacological prophylaxis is expensive and associated with an increased risk of DVT. Compared to the other strategies, SDU screening was associated with better clinical outcomes and lower costs.
Please see later in the article for Editors' Summary
Editors' Summary
Background
For patients who have been seriously injured in an accident or a violent attack (trauma patients), venous thromboembolism (VTE)—the formation of blood clots that limit the flow of blood through the veins—is a frequent and potentially fatal complication. The commonest form of VTE is deep vein thrombosis (DVT). “Distal” DVTs (clots that form in deep veins below the knee) affect about half of patients with severe trauma; “proximal” DVTs (clots that form above the knee) develop in one in five trauma patients. DVTs cause pain and swelling in the affected leg and can leave patients with a painful condition called post-thrombotic syndrome. Worse still, part of the clot can break off and travel to the lungs where it can cause a life-threatening pulmonary embolism (PE). Distal DVTs rarely embolize but, if untreated, half of patients who present with a proximal DVT will develop a PE, and 2%–3% of them will die as a result.
Why Was This Study Done?
VTE is usually prevented by using heparin, a drug that stops blood clotting, but clinicians treating critically ill trauma patients have a dilemma. Many of these patients are at high risk of serious bleeding complications so cannot be given heparin to prevent VTE. Nonpharmacological ways to prevent VTE include the use of pneumatic compression devices to keep the blood moving in the legs (clots often form in patients confined to bed because of the sluggish blood flow in their legs), repeated screening for blood clots using Doppler ultrasound, and the insertion of a “vena cava filter” into the vein that takes blood from the legs to the heart. This last device catches blood clots before they reach the lungs but increases the risk of DVT. Unfortunately, no-one knows which VTE prevention strategy works best in trauma patients who cannot be given heparin. In this study, therefore, the researchers use decision analysis (the systematic evaluation of the most important factors affecting a decision) to estimate the costs and likely clinical outcomes of these strategies.
What Did the Researchers Do and Find?
The researchers used cost and clinical data from patients admitted to a Canadian trauma center with severe head/neck and/or abdomen/pelvis injuries (patients with a high risk of bleeding complications likely to make heparin therapy dangerous for up to two weeks after the injury) to construct a Markov decision analysis model. They then fed published data on the chances of patients developing DVT or PE, and on the effectiveness of the three VTE prevention strategies, into the model to obtain estimates of the costs and clinical outcomes of the strategies at 12 weeks after the injury and over the patients' lifetime. The estimated incidence of DVT at 12 weeks was 15% for the pneumatic compression device and Doppler ultrasound strategies, but 25% for the vena cava filter strategy. By contrast, the estimated incidence of PE was 2.9% with the pneumatic compression device, 1.5% with Doppler ultrasound, but only 0.3% with the vena cava filter. The expected mortality with all three strategies was similar. Finally, the estimated health care costs per patient at 12 weeks were Can$55,334 and Can$55,831 for the Doppler ultrasound and pneumatic compression device strategies, respectively, but Can$57,377 for the vena cava filter strategy; similar trends were seen for lifetime health care costs.
What Do These Findings Mean?
As with all mathematical models, these findings depend on the data fed into the model and on the assumptions included in it. For example, because data from one Canadian trauma unit were used to construct the model, these findings may not be generalizable. Nevertheless, these findings suggest that, although VTE is common among patients with severe injuries, PE is not a major cause of death among these patients. They also suggest that the use of vena cava filters for VTE prevention in patients who cannot receive heparin should not be routinely used because it is expensive and increases the risk of DVT. Finally, these results suggest that, compared with the other strategies, serial Doppler ultrasound is associated with better clinical outcomes and lower costs.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000098.
The US National Heart Lung and Blood Institute provides information (including an animation) on deep vein thrombosis and pulmonary embolism
MedlinePlus provides links to more information about deep vein thrombosis and pulmonary embolism (in several languages)
The UK National Health Service Choices Web site has information on deep vein thrombosis and on embolism (in English and Spanish)
The Eastern Association for the Surgery of Trauma working group document Practice Management Guidelines for the Management of Venous Thromboembolism in Trauma Patients can be downloaded from the Internet
doi:10.1371/journal.pmed.1000098
PMCID: PMC2695771  PMID: 19554085
3.  Association between administered oxygen, arterial partial oxygen pressure and mortality in mechanically ventilated intensive care unit patients 
Critical Care  2008;12(6):R156.
Introduction
The aim of this study was to investigate whether in-hospital mortality was associated with the administered fraction of oxygen in inspired air (FiO2) and achieved arterial partial pressure of oxygen (PaO2).
Methods
This was a retrospective, observational study on data from the first 24 h after admission from 36,307 consecutive patients admitted to 50 Dutch intensive care units (ICUs) and treated with mechanical ventilation. Oxygenation data from all admission days were analysed in a subset of 3,322 patients in 5 ICUs.
Results
Mean PaO2 and FiO2 in the first 24 h after ICU admission were 13.2 kPa (standard deviation (SD) 6.5) and 50% (SD 20%) respectively. Mean PaO2 and FiO2 from all admission days were 12.4 kPa (SD 5.5) and 53% (SD 18). Focusing on oxygenation in the first 24 h of admission, in-hospital mortality was shown to be linearly related to FiO2 value and had a U-shaped relationship with PaO2 (both lower and higher PaO2 values were associated with a higher mortality), independent of each other and of Simplified Acute Physiology Score (SAPS) II, age, admission type, reduced Glasgow Coma Scale (GCS) score, and individual ICU. Focusing on the entire ICU stay, in-hospital mortality was independently associated with mean FiO2 during ICU stay and with the lower two quintiles of mean PaO2 value during ICU stay.
Conclusions
Actually achieved PaO2 values in ICU patients in The Netherlands are higher than generally recommended in the literature. High FiO2, and both low PaO2 and high PaO2 in the first 24 h after admission are independently associated with in-hospital mortality in ICU patients. Future research should study whether this association is causal or merely a reflection of differences in severity of illness insufficiently corrected for in the multivariate analysis.
doi:10.1186/cc7150
PMCID: PMC2646321  PMID: 19077208
4.  Circulating Mitochondrial DNA in Patients in the ICU as a Marker of Mortality: Derivation and Validation 
PLoS Medicine  2013;10(12):e1001577.
In this paper, Choi and colleagues analyzed levels of mitochondrial DNA in two prospective observational cohort studies and found that increased mtDNA levels are associated with ICU mortality, and improve risk prediction in medical ICU patients. The data suggests that mtDNA could serve as a viable plasma biomarker in MICU patients.
Background
Mitochondrial DNA (mtDNA) is a critical activator of inflammation and the innate immune system. However, mtDNA level has not been tested for its role as a biomarker in the intensive care unit (ICU). We hypothesized that circulating cell-free mtDNA levels would be associated with mortality and improve risk prediction in ICU patients.
Methods and Findings
Analyses of mtDNA levels were performed on blood samples obtained from two prospective observational cohort studies of ICU patients (the Brigham and Women's Hospital Registry of Critical Illness [BWH RoCI, n = 200] and Molecular Epidemiology of Acute Respiratory Distress Syndrome [ME ARDS, n = 243]). mtDNA levels in plasma were assessed by measuring the copy number of the NADH dehydrogenase 1 gene using quantitative real-time PCR. Medical ICU patients with an elevated mtDNA level (≥3,200 copies/µl plasma) had increased odds of dying within 28 d of ICU admission in both the BWH RoCI (odds ratio [OR] 7.5, 95% CI 3.6–15.8, p = 1×10−7) and ME ARDS (OR 8.4, 95% CI 2.9–24.2, p = 9×10−5) cohorts, while no evidence for association was noted in non-medical ICU patients. The addition of an elevated mtDNA level improved the net reclassification index (NRI) of 28-d mortality among medical ICU patients when added to clinical models in both the BWH RoCI (NRI 79%, standard error 14%, p<1×10−4) and ME ARDS (NRI 55%, standard error 20%, p = 0.007) cohorts. In the BWH RoCI cohort, those with an elevated mtDNA level had an increased risk of death, even in analyses limited to patients with sepsis or acute respiratory distress syndrome. Study limitations include the lack of data elucidating the concise pathological roles of mtDNA in the patients, and the limited numbers of measurements for some of biomarkers.
Conclusions
Increased mtDNA levels are associated with ICU mortality, and inclusion of mtDNA level improves risk prediction in medical ICU patients. Our data suggest that mtDNA could serve as a viable plasma biomarker in medical ICU patients.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Intensive care units (ICUs, also known as critical care units) are specialist hospital wards that provide care for people with life-threatening injuries and illnesses. In the US alone, more than 5 million people are admitted to ICUs every year. Different types of ICUs treat different types of problems. Medical ICUs treat patients who, for example, have been poisoned or who have a serious infection such as sepsis (blood poisoning) or severe pneumonia (inflammation of the lungs); trauma ICUs treat patients who have sustained a major injury; cardiac ICUs treat patients who have heart problems; and surgical ICUs treat complications arising from operations. Patients admitted to ICUs require constant medical attention and support from a team of specially trained nurses and physicians to prevent organ injury and to keep their bodies functioning. Monitors, intravenous tubes (to supply essential fluids, nutrients, and drugs), breathing machines, catheters (to drain urine), and other equipment also help to keep ICU patients alive.
Why Was This Study Done?
Although many patients admitted to ICUs recover, others do not. ICU specialists use scoring systems (algorithms) based on clinical signs and physiological measurements to predict their patients' likely outcomes. For example, the APACHE II scoring system uses information on heart and breathing rates, temperature, levels of salts in the blood, and other signs and physiological measurements collected during the first 24 hours in the ICU to predict the patient's risk of death. Existing scoring systems are not perfect, however, and “biomarkers” (molecules in bodily fluids that provide information about a disease state) are needed to improve risk prediction for ICU patients. Here, the researchers investigate whether levels of circulating cell-free mitochondrial DNA (mtDNA) are associated with ICU deaths and whether these levels can be used as a biomarker to improve risk prediction in ICU patients. Mitochondria are cellular structures that produce energy. Levels of mtDNA in the plasma (the liquid part of blood) increase in response to trauma and infection. Moreover, mtDNA activates molecular processes that lead to inflammation and organ injury.
What Did the Researchers Do and Find?
The researchers measured mtDNA levels in the plasma of patients enrolled in two prospective observational cohort studies that monitored the outcomes of ICU patients. In the Brigham and Women's Hospital Registry of Critical Illness study, blood was taken from 200 patients within 24 hours of admission into the hospital's medical ICU. In the Molecular Epidemiology of Acute Respiratory Distress Syndrome study (acute respiratory distress syndrome is a life-threatening inflammatory reaction to lung damage or infection), blood was taken from 243 patients within 48 hours of admission into medical and non-medical ICUs at two other US hospitals. Patients admitted to medical ICUs with a raised mtDNA level (3,200 or more copies of a specific mitochondrial gene per microliter of plasma) had a 7- to 8-fold increased risk of dying within 28 days of admission compared to patients with mtDNA levels of less than 3,200 copies/µl plasma. There was no evidence of an association between raised mtDNA levels and death among patients admitted to non-medical ICUs. The addition of an elevated mtDNA level to a clinical model for risk prediction that included the APACHE II score and biomarkers that are already used to predict ICU outcomes improved the net reclassification index (an indicator of the improvement in risk prediction algorithms offered by new biomarkers) of 28-day mortality among medical ICU patients in both studies.
What Do These Findings Mean?
These findings indicate that raised mtDNA plasma levels are associated with death in medical ICUs and show that, among patients in medical ICUs, measurement of mtDNA plasma levels can improve the prediction of the risk of death from the APACHE II scoring system, even when commonly measured biomarkers are taken into account. These findings do not indicate whether circulating cell-free mtDNA increased because of the underlying severity of illness or whether mtDNA actively contributes to the disease process in medical ICU patients. Moreover, they do not provide any evidence that raised mtDNA levels are associated with an increased risk of death among non-medical (mainly surgical) ICU patients. These findings need to be confirmed in additional patients, but given the relative ease and rapidity of mtDNA measurement, the determination of circulating cell-free mtDNA levels could be a valuable addition to the assessment of patients admitted to medical ICUs.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001577.
The UK National Health Service Choices website provides information about intensive care
The Society of Critical Care Medicine provides information for professionals, families, and patients about all aspects of intensive care
MedlinePlus provides links to other resources about intensive care (in English and Spanish)
The UK charity ICUsteps supports patients and their families through recovery from critical illness; its booklet Intensive Care: A Guide for Patients and Families is available in English and ten other languages; its website includes patient experiences and relative experiences of treatment in ICUs
Wikipedia has a page on ICU scoring systems (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
doi:10.1371/journal.pmed.1001577
PMCID: PMC3876981  PMID: 24391478
5.  Respiratory effects of dexmedetomidine in the surgical patient requiring intensive care 
Critical Care  2000;4(5):302-308.
The respiratory effects of dexmedetomidine were retrospectively examined in 33 postsurgical patients involved in a randomised, placebo-controlled trial after extubation in the intensive care unit (ICU). Morphine requirements were reduced by over 50% in patients receiving dexmedetomidine. There were no differences in respiratory rates, oxygen saturations, arterial pH and arterial partial carbon dioxide tension (PaCO2) between the groups. Interestingly the arterial partial oxygen tension (PaO2) : fractional inspired oxygen (FIO2) ratios were statistically significantly higher in the dexmedetomidine group. Dexmedetomidine provides important postsurgical analgesia and appears to have no clinically important adverse effects on respiration in the surgical patient who requires intensive care.
Introduction:
The α2-agonist dexmedetomidine is a new class of sedative drug that is being investigated for use in ICU settings. It is an effective agent for the management of sedation and analgesia after cardiac, general, orthopaedic, head and neck, oncological and vascular surgery in the ICU [1]. Cardiovascular stability was demonstrated, with significant reductions in rate-pressure product during sedation and over the extubation period.
Dexmedetomidine possesses several properties that may additionally benefit those critically ill patients who require sedation. In spontaneously breathing volunteers, intravenous dexmedetomidine caused marked sedation with only mild reductions in resting ventilation at higher doses [2]. Dexmedetomidine reduces the haemodynamic response to intubation and extubation [3,4,5] and attenuates the stress response to surgery [6], as a result of the α2-mediated reduction in sympathetic tone. Therefore, it should be possible to continue sedation with dexmedetomidine over the stressful extubation period without concerns over respiratory depression, while ensuring that haemodynamic stability is preserved.
The present study is a retrospective analysis of the respiratory response to dexmedetomidine in 33 postsurgical patients (who were involved in a randomized, double-blind, placebo-controlled trial [1]) after extubation in the ICU.
Methods:
Patients who participated in the present study were admitted after surgery to our general or cardiothoracic ICUs, and were expected to receive at least 6 h of postsurgical sedation and artificial ventilation.
On arrival in the ICU after surgery, patients were randomized to receive either dexmedetomidine or placebo (normal saline) with rescue sedation and analgesia being provided, only if clinically needed, with midazolam and morphine boluses, respectively. Sedation was titrated to maintain a Ramsay Sedation Score [7] of 3 or greater while the patients were intubated, and infusions of study drug were continued for a maximum of 6 h after extubation to achieve a Ramsay Sedation Score of 2 or greater.
The patients were intubated and ventilated with oxygen-enriched air to attain acceptable arterial blood gases, and extubation occurred when clinically indicated. All patients received supplemental oxygen after extubation, which was delivered by a fixed performance device. Assessment of pain was by direct communication with the patient.
Results are expressed as mean ± standard deviation unless otherwise stated. Patient characteristics, operative details and morphine usage were analyzed using the Mann-Whitney U-test. Statistical differences for respiratory measurements between the two groups were determined using analysis of variance for repeated measures, with the Bonferroni test for post hoc comparisons.
Results:
Of the 40 patients who participated in the study, seven patients could not be included in the analysis of respiratory function because they did not receive a study drug infusion after extubation. Consequently, data from 33 patients are used in the analysis of respiratory function; 16 received dexmedetomidine and 17 placebo. Inadequate arterial blood gas analysis was available in five patients (two from the dexmedetomidine group, and three from the placebo group). There were no significant differences in patient characteristics and operative details between the groups.
Requirements for morphine were reduced by more than 50% in patients receiving dexmedetomidine when compared with placebo after extubation (0.003 ± 0.004 vs 0.008 ± 0.006 mg/kg per h; P= 0.040).
There were no statistically significant differences between placebo and dexmedetomidine for oxygen saturations measured by pulse oximetry (P= 0.26), respiratory rate (P= 0.16; Fig. 1), arterial pH (P= 0.77) and PaCO2 (P= 0.75; Fig. 2) for the 6 h after extubation.
The dexmedetomidine group showed significantly higher PaO2: FIO2 ratios throughout the 6-h intubation (P= 0.036) and extubation (P= 0.037) periods (Fig. 3). There were no adverse respiratory events seen in either the dexmedetomidine or placebo group.
Respiratory rate for the 6-h periods before and after extubation. (Filled circle) Dexmedetomidine; (Empty circle) placebo. Values are expressed as mean ± standard deviation.
PaCO2 (PCO2) for the 6-h periods before and after extubation, and baseline values (B) on admission to ICU immediately after surgery. (Filled circle) Dexmedetomidine; (Empty circle) placebo. Values are expressed as mean ± standard deviation.
PaO2 : FIO2 ratio for the 6-h periods before and after extubation, and baseline values (B) on admission to ICU immediately after surgery. (Filled circle) Dexmedetomidine; (Empty circle) placebo. Values are expressed as mean ± standard deviation.
Discussion:
Lack of respiratory depression in patients sedated with α2-adrenoceptor agonists was first reported by Maxwell [8] in a study investigating the respiratory effects of clonidine. However, more recent data suggests that clonidine may cause mild respiratory depression in humans [9], and α2-adrenoceptor agonists are well known to produce profound intraoperative hypoxaemia in sheep [10,11]. The effects of dexmedetomidine on other ventilation parameters also appear to be species specific [12].
Belleville et al [2] investigated the ventilatory effects of a 2-min intravenous infusion of dexmedetomidine on human volunteers. According to those investigators, minute ventilation and arterial PaCO2 were mildly decreased and increased, respectively. There was a rightward shift and depression of the hypercapnic response with infusions of 1.0 and 2.0 μg/kg.
Previous studies that investigated the respiratory effects of dexmedetomidine have only been performed in healthy human volunteers, who have received either single intramuscular injections or short (= 10 min) intravenous infusions of dexmedetomidine. It is therefore reassuring that no deleterious clinical effects on respiration and gas exchange were seen in the patients we studied, who were receiving long-term infusions. However, there are important limitations to the present results. No dose/response curve for dexmedetomidine can be formulated from the data, and further investigation is probably ethically difficult to achieve in the spontaneously ventilating intensive care patient. We also have no data on the ventilatory responses to hypercapnia and hypoxia, which would also be difficult to examine practically and ethically. The placebo group received more than twice as much morphine as patients receiving dexmedetomidine infusions after extubation, but there were no differences in respiratory rate or PaCO2 between the groups. We can not therefore determine from this study whether dexmedetomidine has any benefits over morphine from a respiratory perspective.
There were no differences in oxygen saturations between the groups because the administered oxygen concentration was adjusted to maintain satisfactory gas exchange. Interestingly, however, there were statistically significant higher PaO2 : FIO2 ratios in the dexmedetomidine group. This ratio allows for the variation in administered oxygen to patients during the study period, and gives some clinical indication of alveolar gas exchange. However, this variable was not a primary outcome variable for the present study, and may represent a type 1 error, although post hoc analysis reveals that the data have 80% power to detect a significant difference (α value 0.05). Further studies are obviously required.
Sedation continued over the extubation period, has been shown to reduce haemodynamic disturbances and myocardial ischaemia [13]. We have previously shown [1] that dexmedetomidine provides cardiovascular stability, with a reduction in rate-pressure product over the extubation period. A sedative agent that has analgesic properties, minimal effects on respiration and offers ischaemia protection would have enormous potential in the ICU. Dexmedetomidine may fulfill all of these roles, but at present we can only conclude that dexmedetomidine has no deleterious clinical effects on respiration when used in doses that are sufficient to provide adequate sedation and effective analgesia in the surgical population requiring intensive care.
PMCID: PMC29047  PMID: 11056756
α2-Adrenoceptor agonist; analgesia; dexmedetomidine; intensive care; postoperative; respiratory; sedation
6.  Prevention and diagnosis of venous thromboembolism in critically ill patients: a Canadian survey 
Critical Care  2001;5(6):336-342.
Background
Venous thromboembolism (VTE) confers considerable morbidity and mortality in hospitalized patients, although few studies have focused on the critically ill population. The objective of this study was to understand current approaches to the prevention and diagnosis of deep venous thrombosis (DVT) and pulmonary embolism (PE) among patients in the intensive care unit (ICU).
Design
Mailed self-administered survey of ICU Directors in Canadian university affiliated hospitals.
Results
Of 29 ICU Directors approached, 29 (100%) participated, representing 44 ICUs and 681 ICU beds across Canada. VTE prophylaxis is primarily determined by individual ICU clinicians (20/29, 69.0%) or with a hematology consultation for challenging patients (9/29, 31.0%). Decisions are usually made on a case-by-case basis (18/29, 62.1%) rather than by preprinted orders (5/29, 17.2%), institutional policies (6/29, 20.7%) or formal practice guidelines (2/29, 6.9%). Unfractionated heparin is the predominant VTE prophylactic strategy (29/29, 100.0%) whereas low molecular weight heparin is used less often, primarily for trauma and orthopedic patients. Use of pneumatic compression devices and thromboembolic stockings is variable. Systematic screening for DVT with lower limb ultrasound once or twice weekly was reported by some ICU Directors (7/29, 24.1%) for specific populations. Ultrasound is the most common diagnostic test for DVT; the reference standard of venography is rarely used. Spiral computed tomography chest scans and ventilation–perfusion scans are used more often than pulmonary angiograms for the diagnosis of PE. ICU Directors recommend further studies in the critically ill population to determine the test properties and risk:benefit ratio of VTE investigations, and the most cost-effective methods of prophylaxis in medical–surgical ICU patients.
Interpretation
Unfractionated subcutaneous heparin is the predominant VTE prophylaxis strategy for critically ill patients, although low molecular weight heparin is prescribed for trauma and orthopedic patients. DVT is most often diagnosed by lower limb ultrasound; however, several different tests are used to diagnose PE. Fundamental research in critically ill patients is needed to help make practice evidence-based.
PMCID: PMC83855  PMID: 11737922
critical care; deep venous thrombosis; diagnosis; intensive care unit; prevention; pulmonary embolism; thromboembolism
7.  The relation between the incidence of hypernatremia and mortality in patients with severe traumatic brain injury 
Critical Care  2009;13(4):R110.
Introduction
The study was aimed at verifying whether the occurrence of hypernatremia during the intensive care unit (ICU) stay increases the risk of death in patients with severe traumatic brain injury (TBI). We performed a retrospective study on a prospectively collected database including all patients consecutively admitted over a 3-year period with a diagnosis of TBI (post-resuscitation Glasgow Coma Score ≤ 8) to a general/neurotrauma ICU of a university hospital, providing critical care services in a catchment area of about 1,200,000 inhabitants.
Methods
Demographic, clinical, and ICU laboratory data were prospectively collected; serum sodium was assessed an average of three times per day. Hypernatremia was defined as two daily values of serum sodium above 145 mmol/l. The major outcome was death in the ICU after 14 days. Cox proportional-hazards regression models were used, with time-dependent variates designed to reflect exposure over time during the ICU stay: hypernatremia, desmopressin acetate (DDAVP) administration as a surrogate marker for the presence of central diabetes insipidus, and urinary output. The same models were adjusted for potential confounding factors.
Results
We included in the study 130 TBI patients (mean age 52 years (standard deviation 23); males 74%; median Glasgow Coma Score 3 (range 3 to 8); mean Simplified Acute Physiology Score II 50 (standard deviation 15)); all were mechanically ventilated; 35 (26.9%) died within 14 days after ICU admission. Hypernatremia was detected in 51.5% of the patients and in 15.9% of the 1,103 patient-day ICU follow-up. In most instances hypernatremia was mild (mean 150 mmol/l, interquartile range 148 to 152). The occurrence of hypernatremia was highest (P = 0.003) in patients with suspected central diabetes insipidus (25/130, 19.2%), a condition that was associated with increased severity of brain injury and ICU mortality. After adjustment for the baseline risk, the incidence of hypernatremia over the course of the ICU stay was significantly related with increased mortality (hazard ratio 3.00 (95% confidence interval: 1.34 to 6.51; P = 0.003)). However, DDAVP use modified this relation (P = 0.06), hypernatremia providing no additional prognostic information in the instances of suspected central diabetes insipidus.
Conclusions
Mild hypernatremia is associated with an increased risk of death in patients with severe TBI. In a proportion of the patients the association between hypernatremia and death is accounted for by the presence of central diabetes insipidus.
doi:10.1186/cc7953
PMCID: PMC2750153  PMID: 19583864
8.  Outcome of patients with pulmonary embolism admitted to the intensive care unit 
Annals of Thoracic Medicine  2009;4(1):13-16.
BACKGROUND:
Pulmonary embolism (PE) is an important cause of in-hospital mortality. Many patients are admitted to the intensive care unit (ICU) either due to hemodynamic instability or severe hypoxemia. Few reports have addressed the outcome of patients with PE; however, none were from ICUs in the Middle East.
OBJECTIVES:
To describe the demographics, clinical presentation, risk factors and outcome of patients with PE admitted to the medical ICU and to identify possible factors associated with poor prognosis.
MATERIALS AND METHODS:
Data were collected retrospectively by reviewing the records of patients admitted to the medical ICU with primary diagnosis of PE between January 2001 and June 2007. Demographic, clinical, radiological and therapeutic data were collected on admission to ICU.
RESULTS:
Fifty-six patients (43% females) with PE were admitted to the ICU during the study period. Their mean age was 40.6 ± 10.6 years. Seven patients (12.5%) had massive PE with hemodynamic instability and 15 (26.8%) had submassive PE. The remaining patients were admitted due to severe hypoxemia. Recent surgery followed by obesity were the most common risk factors (55.4 and 28.6%, respectively). Four patients with massive PE received thrombolysis because the remaining three had absolute contraindications. Fatal gastrointestinal bleeding occurred in one patient post thrombolysis. Additionally, two patients with massive PE and five with submassive PE died within 72 h of admission to the ICU, resulting in an overall mortality rate of 14%. Nonsurvivors were older and had a higher prevalence of immobility and cerebrovascular diseases compared with survivors.
CONCLUSIONS:
The mortality rate of patients with PE admitted to the ICU in our center was comparable to other published studies. Older age, immobility as well as coexistent cerebrovascular diseases were associated with a worse outcome.
doi:10.4103/1817-1737.44779
PMCID: PMC2700473  PMID: 19561916
Intensive care unit; pulmonary embolism; thrombolytic agents
9.  Does dalteparin PROTECT better than heparin? 
Critical Care  2011;15(6):315.
Expanded abstract
Citation
The PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group: Dalteparin versus Unfractionated Heparin in Critically Ill Patients. N Engl J Med 2011, 364:1305-1314.
Background
It is unclear whether there is a clinically significant advantage to prophylactic low-molecular-weight heparin (LMWH) versus unfractionated heparin (UFH) in mixed medical/surgical critically ill adult patients.
Methods
Objective: To compare once daily dalteparin with twice daily unfractionated heparin for primary prophylaxis of proximal deep venous thrombosis in critically ill adults.
Design: A superiority randomized double-blinded controlled trial from 2006 to 2010 in both medical and surgical ICUs. (ClinicalTrials.gov registration number: NCT00182143)
Setting: Multi-center, international medical and surgical intensive care units (ICUs)
Subjects: Critically ill adults expected to remain in the ICU for at least 3 days.
Intervention: Patients were randomized to either twice daily UFH or daily dalteparin for the duration of ICU admission.
Outcomes: The primary endpoint was proximal leg deep venous thrombosis (DVT), at least three days after randomization, detected on twice weekly screening ultrasound. Secondary endpoints were: any DVT, pulmonary embolism (PE), venous thromboembolism (VTE), death, heparin-induced thrombocytopenia (HIT), major bleeding, and composite death/VTE.
Results
Three thousand seven hundred and forty-six subjects were included in the intention-to-treat analysis. Proximal leg DVT occurred in 96 of 1873 (5.1%) patients randomized to dalteparin versus 109 of 1873 (5.8%) patients randomized to UFH (hazard ratio in the dalteparin group, 0.92; 95% confidence interval [CI], 0.68 to 1.23; P = 0.57). The incidence of PE was 1.3% in the dalteparin group compared to 2.3% in the UFH group (hazard ratio, 0.51; 95% CI, 0.30 to 0.88; P = 0.01). There was no mortality difference and no difference in major bleeding between the two study arms. There was a statistically significant decrease in incidence of HIT in the dalteparin group in the per-protocol analysis, but not in the intention-to-treat analysis.
Limitations
Comparing the incidence of PE was a secondary endpoint and the study was not appropriately powered for this conclusion.
Conclusions
Among critically ill adult patients, dalteparin was not superior to UFH at preventing proximal lower extremity DVTs. There is a suggestion that dalteparin might be superior to UFH at preventing pulmonary embolism but a larger trial is necessary to confirm this result.
doi:10.1186/cc10581
PMCID: PMC3388642  PMID: 22152126
10.  Critically ill patients with 2009 H1N1 infection in an Indian ICU 
Background and Aims:
The 2009 pandemic influenza A (H1N1) has taken its toll across most parts of India. We aimed to study its epidemiology, clinical characteristics and outcomes from an Indian multidisciplinary intensive care unit (ICU).
Materials and Methods:
All patients admitted to our ICU with a flu-like illness and who tested positive for the 2009 H1N1 by reverse -transcriptase polymerase- chain -reaction assay during a 3 month period were prospectively studied.
Results:
Thirty one patients were admitted to the ICU during the study period. Patients were in the younger age group with a median age of 35 years (IQR: 28.2-42.8). Obesity was the commonest risk factor. Twenty six patients (83.9%) required ventilator support; the median duration of ventilator support was 10 days (IQR: 4-22). Severe hypoxemia was the predominant feature in all patients. Circulatory failure requiring vasopressors occurred in 18 (58.1%) patients and acute kidney injury in 6 (3.2%) patients. Twenty six patients were alive at the end of 28 days; subsequently all except one were discharged. The median duration of hospital stay was 15 (IQR: 8-22.5) days. Increasing APACHE II scores were associated with an increased risk of death (Hazard Ratio: 1.1; CI: 1.08 -1.2; P = 0.04). Mean tidal volumes in non-survivors were significantly lower; this was related to poor lung compliance in this group.
Conclusions:
2009 H1N1 infection caused severe disease in relatively young patients without significant co-morbidities, characterized by severe hypoxemia and the requirement for prolonged mechanical ventilation. Extra-pulmonary organ failure included circulatory and renal failure.
doi:10.4103/0972-5229.68220
PMCID: PMC2936736  PMID: 20859491
H1N1; influenza; virus; intensive care
11.  Factors influencing physical functional status in intensive care unit survivors two years after discharge 
BMC Anesthesiology  2013;13:11.
Background
Studies suggest that in patients admitted to intensive care units (ICU), physical functional status (PFS) improves over time, but does not return to the same level as before ICU admission. The goal of this study was to assess physical functional status two years after discharge from an ICU and to determine factors influencing physical status in this population.
Methods
The study reviewed all patients admitted to two non-trauma ICUs during a one-year period and included patients with age ≥ 18 yrs, ICU stay ≥ 24 h, and who were alive 24 months after ICU discharge. To assess PFS, Karnofsky Performance Status Scale scores and Lawton-Instrumental Activities of Daily Living (IADL) scores at ICU admission (K-ICU and L-ICU) were compared to the scores at the end of 24 months (K-24mo and L-24mo). Data at 24 months were obtained through telephone interviews.
Results
A total of 1,216 patients were eligible for the study. Twenty-four months after ICU discharge, 499 (41.6%) were alive, agreed to answer the interview, and had all hospital data available. PFS (K-ICU: 86.6 ± 13.8 vs. K-24mo: 77.1 ± 19.6, p < 0.001) and IADL (L-ICU: 27.0 ± 11.7 vs. L-24mo: 22.5 ± 11.5, p < 0.001) declined in patients with medical and unplanned surgical admissions. Most strikingly, the level of dependency increased in neurological patients (K-ICU: 86 ± 12 vs. K-24mo: 64 ± 21, relative risk [RR] 2.6, 95% CI, 1.8–3.6, p < 0.001) and trauma patients (K-ICU: 99 ± 2 vs. K-24mo: 83 ± 21, RR 2.7, 95% CI, 1.6–4.6, p < 0.001). The largest reduction in the ability to perform ADL occurred in neurological patients (L-ICU: 27 ± 7 vs. L-24mo: 15 ± 12, RR 3.3, 95% CI, 2.3–4.6 p < 0.001), trauma patients (L-ICU: 32 ± 0 vs. L-24mo: 25 ± 11, RR 2.8, 95% CI, 1.5–5.1, p < 0.001), patients aged ≥ 65 years (RR 1.4, 95% CI, 1.07–1.86, p = 0.01) and those who received mechanical ventilation for ≥ 8 days (RR 1.48, 95% CI, 1.02–2.15, p = 0.03).
Conclusions
Twenty-four months after ICU discharge, PFS was significantly poorer in patients with neurological injury, trauma, age ≥ 65 tears, and mechanical ventilation ≥ 8 days. Future studies should focus on the relationship between PFS and health-related quality of life in this population.
doi:10.1186/1471-2253-13-11
PMCID: PMC3701489  PMID: 23773812
Activities of Daily Living; Physical Functional Status; Intensive Care Unit; Long-term Care; Mortality; Prognosis; Health-related Quality of Life
12.  AB 68. Post-traumatic lung pseudocysts: two case reports in ICU patients 
Journal of Thoracic Disease  2012;4(Suppl 1):AB68.
Background
The traumatic lung pseudocyst is a rare complication of closed thoracic injury in which increased pressure on pulmonary parenchyma causes laceration (shearing) of the parenchyma without rupture of the pleura. We present two cases with traumatic lung pseudocyst who were admitted in our ICU. Brief review of this entity.
Patients and methods: Case 1
A 19 years old man was admitted in the ICU after a motorcycle accident. Cerebral computed tomography (CT) showed left epidural hematoma. Chest CT scanning revealed two well defined densities in the right upper lung lobe with presence of air bubbles within them and ground glass appearance of the pulmonary parenchyma.The patient was operated by neurosurgeons in order to remove the epidural hematoma. Four days after admission chest CT was repeated and showed two cavitary lesions in the upper lobe with tree in bud sign in the rear section of the right lower lobe. Two samples of bronchial secretions were collected: Ziehl Nilsen staining, gene probe test for M. tuberculosis and culture for mycobacterium tuberculosis were negative. Mantoux test was negative.These findings were compatible with the diagnosis of traumatic pseudocyst. The patient showed gradual clinical improvement. Repeated chest CT scan after 6 months was within normal limits. Case 2. A 41 years old man was involved in a car-bicycle accident (he was riding the bicycle). The patient was admitted in the ICU with respiratory failure and flail chest. Chest CT scanning revealed subcutaneous emphysema, multiple bilateral rib fractures, fracture of the right clavicle, fracture of the sternum, right pneumothorax, bilateral hemothorax, and contusions of the right lung. The next day the patient was intubated because of progressive respiratory failure. Two days after admission chest CT was repeated and showed formation of lung pseudocyst, remaining pneumothorax and hemothorax. The clinical course was complicated with febrile respiratory infection and haemodynamic instability. He was treated with broad spectrum antibiotics. The patient was gradually stabilised and finally was weaned from mechanical ventilation (with a tracheostomy). 22 days after the accident the chest CT revealed resolution of the pseudocysts, and bilateral pleural effusion.
Conclusions
The traumatic lung pseudocyst is a rare complication of blunt thoracic trauma. The clinical course of traumatic lung pseudocyst is usually benign, requiring only supportive therapy, unless complications such as pneumothorax or infection of the cavitary lesion arise. These lesions are more common in children and young adults.
doi:10.3978/j.issn.2072-1439.2012.s068
PMCID: PMC3537347
13.  Admission factors associated with hospital mortality in patients with haematological malignancy admitted to UK adult, general critical care units: a secondary analysis of the ICNARC Case Mix Programme Database 
Critical Care  2009;13(4):R137.
Introduction
Patients with haematological malignancy admitted to intensive care have a high mortality. Adverse prognostic factors include the number of organ failures, invasive mechanical ventilation and previous bone marrow transplantation. Severity-of-illness scores may underestimate the mortality of critically ill patients with haematological malignancy. This study investigates the relationship between admission characteristics and outcome in patients with haematological malignancies admitted to intensive care units (ICUs) in England, Wales and Northern Ireland, and assesses the performance of three severity-of-illness scores in this population.
Methods
A secondary analysis of the Intensive Care National Audit and Research Centre (ICNARC) Case Mix Programme Database was conducted on admissions to 178 adult, general ICUs in England, Wales and Northern Ireland between 1995 and 2007. Multivariate logistic regression analysis was used to identify factors associated with hospital mortality. The Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II and ICNARC score were evaluated for discrimination (the ability to distinguish survivors from nonsurvivors); and the APACHE II, SAPS II and ICNARC mortality probabilities were evaluated for calibration (the accuracy of the estimated probability of survival).
Results
There were 7,689 eligible admissions. ICU mortality was 43.1% (3,312 deaths) and acute hospital mortality was 59.2% (4,239 deaths). ICU and hospital mortality increased with the number of organ failures on admission. Admission factors associated with an increased risk of death were bone marrow transplant, Hodgkin's lymphoma, severe sepsis, age, length of hospital stay prior to intensive care admission, tachycardia, low systolic blood pressure, tachypnoea, low Glasgow Coma Score, sedation, PaO2:FiO2, acidaemia, alkalaemia, oliguria, hyponatraemia, hypernatraemia, low haematocrit, and uraemia. The ICNARC model had the best discrimination of the three scores analysed, as assessed by the area under the receiver operating characteristic curve of 0.78, but all scores were poorly calibrated. APACHE II had the highest accuracy at predicting hospital mortality, with a standardised mortality ratio of 1.01. SAPS II and the ICNARC score both underestimated hospital mortality.
Conclusions
Increased hospital mortality is associated with the length of hospital stay prior to ICU admission and with severe sepsis, suggesting that, if appropriate, such patients should be treated aggressively with early ICU admission. A low haematocrit was associated with higher mortality and this relationship requires further investigation. The severity-of-illness scores assessed in this study had reasonable discriminative power, but none showed good calibration.
doi:10.1186/cc8016
PMCID: PMC2750195  PMID: 19706163
14.  Sex-and age-based differences in the delivery and outcomes of critical care 
Background
Previous studies have suggested that a patient's sex may influence the provision and outcomes of critical care. Our objective was to determine whether sex and age are associated with differences in admission practices, processes of care and clinical outcomes for critically ill patients.
Methods
We used a retrospective cohort of 466 792 patients, including 24 778 critically ill patients, admitted consecutively to adult hospitals in Ontario between Jan. 1, 2001, and Dec. 31, 2002. We measured associations between sex and age and admission to the intensive care unit (ICU); use of mechanical ventilation, dialysis or pulmonary artery catheterization; length of stay in the ICU and hospital; and death in the ICU, hospital and 1 year after admission.
Results
Of the 466 792 patients admitted to hospital, more were women than men (57.0% v. 43.0% for all admissions, p < 0.001; 50.1% v. 49.9% for nonobstetric admissions, p < 0.001). However, fewer women than men were admitted to ICUs (39.9% v. 60.1%, p < 0.001); this difference was most pronounced among older patients (age ≥ 50 years). After adjustment for admission diagnoses and comorbidities, older women were less likely than older men to receive care in an ICU setting (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.66–0.71). After adjustment for illness severity, older women were also less likely than older men to receive mechanical ventilation (OR 0.91, 95% CI 0.81– 0.97) or pulmonary artery catheterization (OR 0.80, 95% CI 0.73– 0.88). Despite older men and women having similar severity of illness on ICU admission, women received ICU care for a slightly shorter duration yet had a longer length of stay in hospital (mean 18.3 v. 16.9 days; p = 0.006). After adjustment for differences in comorbidities, source of admission, ICU admission diagnosis and illness severity, older women had a slightly greater risk of death in the ICU (hazard ratio 1.20, 95% CI 1.10–1.31) and in hospital (hazard ratio 1.08, 95% CI 1.00–1.16) than did older men.
Interpretation
Among patients 50 years or older, women appear less likely than men to be admitted to an ICU and to receive selected life-supporting treatments and more likely than men to die after critical illness. Differences in presentation of critical illness, decision-making or unmeasured confounding factors may contribute to these findings.
doi:10.1503/cmaj.071112
PMCID: PMC2096494  PMID: 18003954
15.  Clinically important deep vein thrombosis in the intensive care unit: a survey of intensivists 
Critical Care  2004;8(3):R145-R152.
Introduction
Outside the intensive care unit (ICU), clinically important deep vein thrombosis (DVT) is usually defined as a symptomatic event that leads to objective radiologic confirmation and subsequent treatment. The objective of the present survey is to identify the patient factors and radiologic features of lower limb DVT that intensivists consider more or less likely to make a DVT clinically important in ICU patients.
Methods
Our definition of clinically important DVT was a DVT likely to result in short-term or long-term morbidity or mortality if left untreated, as opposed to a DVT that is unlikely to have important consequences. We asked respondents to indicate the likelihood that patient factors and ultrasonographic features make a DVT clinically important using a five-point scale (from 1 = much less likely to 5 = much more likely).
Results
Of the 71 Canadian intensivists who responded, 70 (99%) rated three patient factors as most likely to make a DVT clinically important: clinical suspicion of pulmonary embolism (mean score 4.6), acute or chronic cardiopulmonary morbidity that might limit a patient's ability to tolerate pulmonary embolism (score 4.5), and leg symptoms (score 4.2). Of the ultrasound features, proximal (score 4.7), large (score 4.2), and totally occlusive (score 3.9) thrombi were considered the three most important.
Conclusion
When labeling a DVT as clinically important, intensivists rely on different patient specific factors and thrombus characteristics than are used to assess the clinical importance of DVT outside the ICU. The clinical importance of DVT is influenced by unique factors such as cardiopulmonary reserve among mechanically ventilated patients.
doi:10.1186/cc2859
PMCID: PMC468908  PMID: 15153243
deep venous thrombosis; pulmonary embolism; ultrasound
16.  Differences in the prognosis among severe trauma and medical patients requiring mechanical ventilation 
Objetive. To find the differences between the prognosis of the patients with severe traumatism injury and those who were admitted with medical pathology who also required mechanical ventilation in our ICU. Patients and Method. Retrospective descriptive study in a polyvalent ICU of a third level hospital for a period of 8 years. Epidemiological variables such as age, sex, average stay, mortality, APACHE II at admission and days of mechanical ventilation, were analyzed in patients with severe traumatism injury and patients with medical pathology that were admitted in ICU and received mechanical ventilation during this period. Results. During the study period were admitted 208 patients with severe traumatism injury and 732 medical patients, all of them required mechanical ventilation. Patients with severe traumatism injury are more younger (41.8 vs 55.3 years, p = 0.001) and entered ICU in a state of minor severity, according to the prognostic index APACHE II (14.8 vs 17.4, p < 0.001), despite which they required more days of mechanical ventilation (9.8 vs 7.8 days, p = 0.017) and had a higher average stay (11.4 vs 9.4 days, p = 0.027), although the mortality was significantly lower (38.2% vs 28.2%, p = 0.005). Multivariate analysis showed as independent variables associated with mortality, the APACHE II (p < 0.0001), the average stay in ICU (p < 0.0001), days of mechanical ventilation (p < 0.0001) and type patient (p = 0.016). Conclusions. Patients with severe traumatic injury that require mechanical ventilation despite to be admitted in ICU in a state of greater severity, having an increased ICU stay and more days of mechanical ventilation, have a better prognosis than medical patients that required also mechanical ventilation at ICU stay, likely to be younger.
PMCID: PMC3828737  PMID: 24273698
Respiration; artificial; multiple trauma; patients; outcome assessment
17.  Risk stratification of early admission to the intensive care unit of patients with no major criteria of severe community-acquired pneumonia: development of an international prediction rule 
Critical Care  2009;13(2):R54.
Introduction
To identify risk factors for early (< three days) intensive care unit (ICU) admission of patients hospitalised with community-acquired pneumonia (CAP) and not requiring immediate ICU admission, and to stratify the risk of ICU admission on days 1 to 3.
Methods
Using the original data from four North American and European prospective multicentre cohort studies of patients with CAP, we derived and validated a prediction rule for ICU admission on days 1 to 3 of emergency department (ED) presentation, for patients presenting with no obvious reason for immediate ICU admission (not requiring immediate respiratory or circulatory support).
Results
A total of 6560 patients were included (4593 and 1967 in the derivation and validation cohort, respectively), 303 (4.6%) of whom were admitted to an ICU on days 1 to 3. The Risk of Early Admission to ICU index (REA-ICU index) comprised 11 criteria independently associated with ICU admission: male gender, age younger than 80 years, comorbid conditions, respiratory rate of 30 breaths/minute or higher, heart rate of 125 beats/minute or higher, multilobar infiltrate or pleural effusion, white blood cell count less than 3 or 20 G/L or above, hypoxaemia (oxygen saturation < 90% or arterial partial pressure of oxygen (PaO2) < 60 mmHg), blood urea nitrogen of 11 mmol/L or higher, pH less than 7.35 and sodium less than 130 mEq/L. The REA-ICU index stratified patients into four risk classes with a risk of ICU admission on days 1 to 3 ranging from 0.7 to 31%. The area under the curve was 0.81 (95% confidence interval (CI) = 0.78 to 0.83) in the overall population.
Conclusions
The REA-ICU index accurately stratifies the risk of ICU admission on days 1 to 3 for patients presenting to the ED with CAP and no obvious indication for immediate ICU admission and therefore may assist orientation decisions.
doi:10.1186/cc7781
PMCID: PMC2689501  PMID: 19358736
18.  A predictive model for the early identification of patients at risk for a prolonged intensive care unit length of stay 
Background
Patients with a prolonged intensive care unit (ICU) length of stay account for a disproportionate amount of resource use. Early identification of patients at risk for a prolonged length of stay can lead to quality enhancements that reduce ICU stay. This study developed and validated a model that identifies patients at risk for a prolonged ICU stay.
Methods
We performed a retrospective cohort study of 343,555 admissions to 83 ICUs in 31 U.S. hospitals from 2002-2007. We examined the distribution of ICU length of stay to identify a threshold where clinicians might be concerned about a prolonged stay; this resulted in choosing a 5-day cut-point. From patients remaining in the ICU on day 5 we developed a multivariable regression model that predicted remaining ICU stay. Predictor variables included information gathered at admission, day 1, and ICU day 5. Data from 12,640 admissions during 2002-2005 were used to develop the model, and the remaining 12,904 admissions to internally validate the model. Finally, we used data on 11,903 admissions during 2006-2007 to externally validate the model.
Results
The variables that had the greatest impact on remaining ICU length of stay were those measured on day 5, not at admission or during day 1. Mechanical ventilation, PaO2: FiO2 ratio, other physiologic components, and sedation on day 5 accounted for 81.6% of the variation in predicted remaining ICU stay. In the external validation set observed ICU stay was 11.99 days and predicted total ICU stay (5 days + day 5 predicted remaining stay) was 11.62 days, a difference of 8.7 hours. For the same patients, the difference between mean observed and mean predicted ICU stay using the APACHE day 1 model was 149.3 hours. The new model's r2 was 20.2% across individuals and 44.3% across units.
Conclusions
A model that uses patient data from ICU days 1 and 5 accurately predicts a prolonged ICU stay. These predictions are more accurate than those based on ICU day 1 data alone. The model can be used to benchmark ICU performance and to alert physicians to explore care alternatives aimed at reducing ICU stay.
doi:10.1186/1472-6947-10-27
PMCID: PMC2876991  PMID: 20465830
19.  Indicators of the need for ICU admission following suicide bombing attacks 
Introduction
Critical hospital resources, especially the demand for ICU beds, are usually limited following mass casualty incidents such as suicide bombing attacks (SBA). Our primary objective was to identify easily diagnosed external signs of injury that will serve as indicators of the need for ICU admission. Our secondary objective was to analyze under- and over-triage following suicidal bombing attacks.
Methods
A database was collected prospectively from patients who were admitted to Hadassah University Hospital Level I Trauma Centre, Jerusalem, Israel from August 2001-August 2005 following a SBA. One hundred and sixty four victims of 17 suicide bombing attacks were divided into two groups according to ICU and non-ICU admission.
Results
There were 86 patients in the ICU group (52.4%) and 78 patients in the non-ICU group (47.6%). Patients in the ICU group required significantly more operating room time compared with patients in the non-ICU group (59.3% vs. 25.6%, respectively, p = 0.0003). For the ICU group, median ICU stay was 4 days (IQR 2 to 8.25 days). On multivariable analysis only the presence of facial fractures (p = 0.014), peripheral vascular injury (p = 0.015), injury ≥ 4 body areas (p = 0.002) and skull fractures (p = 0.017) were found to be independent predictors of the need for ICU admission. Sixteen survivors (19.5%) in the ICU group were admitted to the ICU for one day only (ICU-LOS = 1) and were defined as over-triaged. Median ISS for this group was significantly lower compared with patients who were admitted to the ICU for > 1 day (ICU-LOS > 1). This group of over-triaged patients could not be distinguished from the other ICU patients based on external signs of trauma. None of the patients in the non-ICU group were subsequently transferred to the ICU.
Conclusions
Our results show that following SBA, injury to ≥ 4 areas, and certain types of injuries such as facial and skull fractures, and peripheral vascular injury, can serve as surrogates of severe trauma and the need for ICU admission. Over-triage rates following SBA can be limited by a concerted, focused plan implemented by dedicated personnel and by the liberal utilization of imaging studies.
doi:10.1186/1757-7241-20-19
PMCID: PMC3313896  PMID: 22405507
Blast injury; Suicidal attacks; Intensive care unit; Triage
20.  Venous thromboembolism and bleeding in critically ill patients with severe renal insufficiency receiving dalteparin thromboprophylaxis: prevalence, incidence and risk factors 
Critical Care  2008;12(2):R32.
Background
Critically ill patients with renal insufficiency are predisposed to both deep vein thrombosis (DVT) and bleeding. The objective of the present study was to evaluate the prevalence, incidence and predictors of DVT and the incidence of bleeding in intensive care unit (ICU) patients with estimated creatinine clearance <30 ml/min.
Methods
In a multicenter, open-label, prospective cohort study of critically ill patients with severe acute or chronic renal insufficiency or dialysis receiving subcutaneous dalteparin 5,000 IU once daily, we estimated the prevalence of proximal DVT by screening compression venous ultrasound of the lower limbs within 48 hours of ICU admission. DVT incidence was assessed on twice-weekly ultrasound testing. We estimated the incidence of major and minor bleeding by daily clinical assessments. We used Cox proportional hazards regression to identify independent predictors of both DVT and major bleeding.
Results
Of 156 patients with a mean (standard deviation) creatinine clearance of 18.9 (6.5) ml/min, 18 had DVT or pulmonary embolism within 48 hours of ICU admission, died or were discharged before ultrasound testing – leaving 138 evaluable patients who received at least one dose of dalteparin. The median duration of dalteparin administration was 7 days (interquartile range, 4 to 12 days). DVT developed in seven patients (5.1%; 95% confidence interval, 2.5 to 10.1). The only independent risk factor for DVT was an elevated baseline Acute Physiology and Chronic Health Evaluation II score (hazard ratio for 10-point increase, 2.25; 95% confidence interval, 1.03 to 4.91). Major bleeding developed in 10 patients (7.2%; 95% confidence interval, 4.0 to 12.8), all with trough anti-activated factor X levels ≤ 0.18 IU/ml. Independent risk factors for major bleeding were aspirin use (hazard ratio, 6.30; 95% confidence interval, 1.35 to 29.4) and a high International Normalized Ratio (hazard ratio for 0.5-unit increase, 1.68; 95% confidence interval, 1.07 to 2.66).
Conclusion
In ICU patients with renal insufficiency, the incidence of DVT and major bleeding are considerable but appear related to patient comorbidities rather than to an inadequate or excessive anticoagulant from thromboprophylaxis with dalteparin.
Clinical Trial Registration
Number NCT00138099.
doi:10.1186/cc6810
PMCID: PMC2447552  PMID: 18315876
21.  Variability of ICU Use in Adult Patients With Minor Traumatic Intracranial Hemorrhage 
Annals of emergency medicine  2012;61(5):10.1016/j.annemergmed.2012.08.024.
Study objective
Patients with minor traumatic intracranial hemorrhage are frequently admitted to the ICU, although many never require critical care interventions. To describe ICU resource use in minor traumatic intracranial hemorrhage, we assess (1) the variability of ICU use in a cohort of patients with minor traumatic intracranial hemorrhage across multiple trauma centers, and (2) the proportion of adult patients with traumatic intracranial hemorrhage who are admitted to the ICU and never receive a critical care intervention during hospitalization. In addition, we evaluate the association between ICU admission and key independent variables.
Methods
A structured, historical cohort study of adult patients (aged 18 years and older) with minor traumatic intracranial hemorrhage was conducted within a consortium of 8 Level I trauma centers in the western United States from January 2005 to June 2010. The study population included patients with minor traumatic intracranial hemorrhage, defined as an emergency department (ED) Glasgow Coma Scale (GCS) score of 15 (normal mental status) and an Injury Severity Score less than 16 (no other major organ injury). The primary outcome measure was initial ICU admission. The secondary outcome measure was a critical care intervention during hospitalization. Critical care interventions included mechanical ventilation, neurosurgical intervention, transfusion of blood products, vasopressor or inotrope administration, and invasive hemodynamic monitoring. ED disposition and the proportion of ICU patients not receiving a critical care intervention were compared across sites with descriptive statistics. The association between ICU admission and predetermined independent variables was analyzed with multivariable regression.
Results
Among 11,240 adult patients with traumatic intracranial hemorrhage, 1,412 (13%) had minor traumatic intracranial hemorrhage and complete ED disposition data (mean age 48 years; SD 20 years). ICU use within this cohort across sites ranged from 50% to 97%. Overall, 847 of 888 patients (95%) with minor traumatic intracranial hemorrhage who were admitted to the ICU did not receive a critical care intervention during hospitalization (range between sites 80% to 100%). Three of 524 (0.6%) patients discharged home or admitted to the observation unit or ward received a critical care intervention. After controlling for severity of injury (age, blood pressure, and Injury Severity Score), study site was independently associated with ICU admission (odds ratios ranged from 1.5 to 30; overall effect P<.001).
Conclusion
Across a consortium of trauma centers in the western United States, there was wide variability in ICU use within a cohort of patients with minor traumatic intracranial hemorrhage. Moreover, a large proportion of patients admitted to the ICU never required a critical care intervention, indicating the potential to improve use of critical care resources in patients with minor traumatic intracranial hemorrhage.
doi:10.1016/j.annemergmed.2012.08.024
PMCID: PMC3880139  PMID: 23021347
22.  Thromboprophylaxis patterns and determinants in critically ill patients: a multicenter audit 
Critical Care  2014;18(2):R82.
Introduction
Heparin is safe and prevents venous thromboembolism in critical illness. We aimed to determine the guideline concordance for thromboprophylaxis in critically ill patients and its predictors, and to analyze factors associated with the use of low molecular weight heparin (LMWH), as it may be associated with a lower risk of pulmonary embolism and heparin-induced thrombocytopenia without increasing the bleeding risk.
Methods
We performed a retrospective audit in 28 North American intensive care units (ICUs), including all consecutive medical-surgical patients admitted in November 2011. We documented ICU thromboprophylaxis and reasons for omission. Guideline concordance was determined by adding days in which patients without contraindications received thromboprophylaxis to days in which patients with contraindications did not receive it, divided by the total number of patient-days. We used multilevel logistic regression including time-varying, center and patient-level covariates to determine the predictors of guideline concordance and use of LMWH.
Results
We enrolled 1,935 patients (62.3 ± 16.7 years, Acute Physiology and Chronic Health Evaluation [APACHE] II score 19.1 ± 8.3). Patients received thromboprophylaxis with unfractionated heparin (UFH) (54.0%) or LMWH (27.6%). Guideline concordance occurred for 95.5% patient-days and was more likely in patients who were sicker (odds ratio (OR) 1.49, 95% confidence interval (CI) 1.17, 1.75 per 10-point increase in APACHE II), heavier (OR 1.32, 95% CI 1.05, 1.65 per 10-m/kg2 increase in body mass index), had cancer (OR 3.22, 95% CI 1.81, 5.72), previous venous thromboembolism (OR 3.94, 95% CI 1.46,10.66), and received mechanical ventilation (OR 1.83, 95% CI 1.32,2.52). Reasons for not receiving thromboprophylaxis were high risk of bleeding (44.5%), current bleeding (16.3%), no reason (12.9%), recent or upcoming invasive procedure (10.2%), nighttime admission or discharge (9.7%), and life-support limitation (6.9%). LMWH was less often administered to sicker patients (OR 0.65, 95% CI 0.48, 0.89 per 10-point increase in APACHE II), surgical patients (OR 0.41, 95% CI 0.24, 0.72), those receiving vasoactive drugs (OR 0.47, 95% CI 0.35, 0.64) or renal replacement therapy (OR 0.10, 95% CI 0.05, 0.23).
Conclusions
Guideline concordance for thromboprophylaxis was high, but LMWH was less commonly used, especially in patients who were sicker, had surgery, or received vasopressors or renal replacement therapy, representing a potential quality improvement target.
doi:10.1186/cc13844
PMCID: PMC4057024  PMID: 24766968
23.  Early tracheostomy in intensive care trauma patients improves resource utilization: a cohort study and literature review 
Critical Care  2004;8(5):R347-R352.
Introduction
Despite the integral role played by tracheostomy in the management of trauma patients admitted to intensive care units (ICUs), its timing remains subject to considerable practice variation. The purpose of this study is to examine the impact of early tracheostomy on the duration of mechanical ventilation, ICU length of stay, and outcomes in trauma ICU patients.
Methods
The following data were obtained from a prospective ICU database containing information on all trauma patients who received tracheostomy over a 5-year period: demographics, Acute Physiology and Chronic Health Evaluation II score, Simplified Acute Physiology Score II, Glasgow Coma Scale score, Injury Severity Score, type of injuries, ICU and hospital outcomes, ICU and hospital length of stay (LOS), and the type of tracheostomy procedure (percutaneous versus surgical). Tracheostomy was considered early if it was performed by day 7 of mechanical ventilation. We compared the duration of mechanical ventilation, ICU LOS and outcome between early and late tracheostomy patients. Multivariate analysis was performed to assess the impact of tracheostomy timing on ICU stay.
Results
Of 653 trauma ICU patients, 136 (21%) required tracheostomies, 29 of whom were early and 107 were late. Age, sex, Acute Physiology and Chronic Health Evaluation II score, Simplified Acute Physiology Score II and Injury Severity Score were not different between the two groups. Patients with early tracheostomy were more likely to have maxillofacial injuries and to have lower Glasgow Coma Scale score. Duration of mechanical ventilation was significantly shorter with early tracheostomy (mean ± standard error: 9.6 ± 1.2 days versus 18.7 ± 1.3 days; P < 0.0001). Similarly, ICU LOS was significantly shorter (10.9 ± 1.2 days versus 21.0 ± 1.3 days; P < 0.0001). Following tracheostomy, patients were discharged from the ICU after comparable periods in both groups (4.9 ± 1.2 days versus 4.9 ± 1.1 days; not significant). ICU and hospital mortality rates were similar. Using multivariate analysis, late tracheostomy was an independent predictor of prolonged ICU stay (>14 days).
Conclusion
Early tracheostomy in trauma ICU patients is associated with shorter duration of mechanical ventilation and ICU LOS, without affecting ICU or hospital outcome. Adopting a standardized strategy of early tracheostomy in appropriately selected patients may help in reducing unnecessary resource utilization.
doi:10.1186/cc2924
PMCID: PMC1065024  PMID: 15469579
intensive care; mechanical ventilation; resource utilization; Saudi Arabia; trauma; tracheostomy; weaning
24.  Case mix, outcome and activity for patients admitted to intensive care units requiring chronic renal dialysis: a secondary analysis of the ICNARC Case Mix Programme Database 
Critical Care  2007;11(2):R50.
Introduction
This report describes the case mix, outcome and activity for admissions to intensive care units (ICUs) of patients who require prior chronic renal dialysis for end-stage renal failure (ESRF), and investigates the effect of case mix factors on outcome.
Methods
This was a secondary analysis of a high-quality clinical database, namely the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme Database, which includes 276,731 admissions to 170 adult ICUs across England, Wales and Northern Ireland from 1995 to 2004.
Results
During the eight year study period, 1.3% (n = 3,420) of all patients admitted to ICU were receiving chronic renal dialysis before ICU admission. This represents an estimated ICU utilization of six admissions (32 bed-days) per 100 dialysis patient-years. The ESRF group was younger (mean age 57.3 years versus 59.5 years) and more likely to be male (60.2% versus 57.9%) than those without ESRF. Acute Physiology and Chronic Health Evaluation II score and Acute Physiology Score revealed greater severity of illness on admission in patients with ESRF (mean 24.7 versus 16.6 and 17.2 versus 12.6, respectively). Length of stay in ICU was comparable between groups (median 1.9 days versus 1.8 days) and ICU mortality was only slightly elevated in the ESRF group (26.3% versus 20.8%). However, the ESRF group had protracted overall hospital stay (median 25 days versus 17 days), and increased hospital mortality (45.3% versus 31.2%) and ICU readmission (9.0% vs. 4.7%). Multiple logistic regression analysis adjusted for case mix identified the increased hospital mortality to be associated with increasing age, emergency surgery and nonsurgical cases, cardiopulmonary resuscitation before ICU admission and extremes of physiological norms. The adjusted odds ratio for ultimate hospital mortality associated with chronic renal dialysis was 1.24 (95% confidence interval 1.13 to 1.37).
Conclusion
Patients with ESRF admitted to UK ICUs are more likely to be male and younger, with a medical cause of admission, and to have greater severity of illness than the non-ESRF population. Outcomes on the ICU were comparable between the two groups, but those patients with ESRF had greater readmission rates, prolonged post-ICU hospital stay and increased post-ICU hospital mortality. This study is by far the largest comparative outcome analysis to date in patients with ESRF admitted to the ICU. It may help to inform clinical decision-making and resource requirements for this patient population.
doi:10.1186/cc5785
PMCID: PMC2206479  PMID: 17451605
25.  Implementation, reliability testing, and compliance monitoring of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) in trauma patients 
Intensive care medicine  2008;34(7):1263-1268.
Objective
To implement delirium monitoring, test reliability, and monitor compliance of performing the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) in trauma patients.
Design and setting
Prospective, observational study in a Level 1 trauma unit of a tertiary care, university-based medical center.
Patients
Acutely injured patients admitted to the trauma unit from February 1, 2006–April 16, 2006.
Measurements and Results
Following web-based teaching modules and group in-services, bedside nurses evaluated patients daily for depth of sedation with the Richmond Agitation-Sedation Scale (RASS) and for the presence of delirium with the CAM-ICU. On randomly assigned days over a 10-week period, evaluations by nursing staff were followed by evaluations by an expert evaluator of the RASS and the CAM-ICU, in order to assess compliance and reliability of the CAM-ICU in trauma patients. Following the audit period, the nurses completed a post-implementation survey.
One thousand and eleven random CAM-ICU assessments were performed by the expert evaluator, within 1 hour of the bedside nurses’ assessments. Nurses completed the CAM-ICU assessments in 84% (849 of 1011) of evaluations. Overall agreement (κ) between nurses and the expert evaluator was 0.77 (0.721, 0.822; p<0.0001). In TBI patients κ was 0.75 (0.667, 0.829; p<0.0001), while in mechanically-ventilated patients κ was 0.62 (0.534, 0.704; p<0.0001). The survey revealed nurses were confident in performing the CAM-ICU, realized the importance of delirium, and were satisfied with the training they received. The survey also acknowledged obstacles to implementation including nursing time and failure of physicians/surgeons to address treatment approaches for delirium.
Conclusions
The CAM-ICU can be successfully implemented in a university-based trauma unit with high compliance and reliability. Quality improvement projects seeking to implement delirium monitoring would be wise to address potential pitfalls including time complaints and the negative impact of physician indifference regarding this form of organ dysfunction.
doi:10.1007/s00134-008-1031-x
PMCID: PMC3773486  PMID: 18297270
delirium; trauma; critical care; implementation; monitoring; Confusion Assessment Method for the Intensive Care Unit (CAM-ICU)

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