John F. Cade

A Prospective Study of the Value of Monitoring Heparin Treatment with the Activated Partial Thromboplastin Time

Abstract Two hundred and thirty-four patients treated with continuous intravenous infusions of heparin were studied prospectively to seek a relation between the activated partial thromboplastin tim...

High risk of the critically ill for venous thromboembolism.

The incidence of deep venous thrombosis of the legs (DVT) was studied in 119 critically ill patients by 125I-labeled fibrinogen scanning; the efficacy of low-dose heparin prophylaxis was assessed in a randomized, double-blind study. DVT occurred in 29% of control patients and in 13% of patients receiving heparin 5000 U subcutaneously twice daily. DVT was found mainly in men and was associated with circulatory impairment, respiratory failure and recent vascular or cancer surgery. In a comparison study of medical patients, DVT occurred in 10% untreated and 2% treated. In conclusion, the critically ill are at high risk of venous thromboembolism and low-dose heparin prophylaxis is warranted in those who have no hemostatic impairment.

Multicenter, double-blind, placebo-controlled study of the use of filgrastim in patients hospitalized with pneumonia and severe sepsis*

ObjectiveTo determine the safety and efficacy of filgrastim (r-metHuG-CSF) in combination with intravenous antibiotics to reduce the rate of mortality in patients with pneumonia and sepsis. DesignThis study was multicenter, double-blind, and randomized. SettingIntensive care units PatientsAdult patients with bacterial pneumonia, either acquired or nosocomial, as confirmed by chest radiograph and positive culture or Gram-negative stain, and severe sepsis, defined as sepsis-induced hypotension or organ dysfunction. InterventionsStandard antibiotic therapy with or without filgrastim (300 &mgr;g/day) or placebo administered as a 30-min intravenous infusion. The study drug was started within 24 hrs of enrollment and was continued for 5 days or until the white blood cell count reached >75.0 × 109 cells/L. Measurements and Main ResultsThe primary end point was the occurrence of mortality through day 29; secondary end points included occurrence of subsequent organ dysfunction, time to discharge from intensive care unit, number of days on mechanical ventilatory support, and time to death. Study-related observations were recorded through day 10 and included vital signs, onset of organ dysfunction, clinical laboratory variables, and adverse events. Filgrastim increased the white blood cell count to a median peak of 31.7 × 109 cells/L from a baseline of 12.3 × 109 cells/L. The two groups were well matched and did not differ significantly with regard to severe adverse events, time to death, occurrence of end-organ dysfunction, days of intensive care unit hospitalization, or days on mechanical ventilatory support. Mortality was low in both treatment groups; the mortality rate in patients with adult respiratory distress syndrome was similar between the two groups. ConclusionsThe addition of filgrastim to the antibiotic and supportive care treatment of patients with pneumonia complicated by severe sepsis appeared to be safe, but not efficacious in reducing mortality rates or complications from this infection.

Epidemiology of sepsis in Victoria, Australia

Objective:To determine the clinical and epidemiologic characteristics of patients with sepsis admitted to hospitals in Victoria, Australia, including the incidence of sepsis and severe sepsis, utilization of intensive care unit (ICU) resources, and hospital mortality. Design:A population-based hospital morbidity database generated from hospital discharge coding. Setting:State of Victoria, Australia (population, 4.5 million), the 4-yr period from July 1, 1999, to June 30, 2003. Patients:A total of 3,122,515 overnight hospitalizations. Interventions:None. Measurements and Main Results:The overall hospital incidence of sepsis was 1.1%, with a mortality of 18.4%. Of septic patients, 23.8% received some care in an ICU. For these patients, hospital mortality was 28.9%. Severe sepsis, defined by sepsis and at least one organ dysfunction, occurred in 39% of sepsis patients and was accompanied by a hospital mortality of 31.1%. Fifty percent of patients with severe sepsis received at least some care in an ICU. Conclusions:Australian state hospital administrative data reveal epidemiologic features of sepsis and severe sepsis that are strikingly similar to those recently reported from comparable populations in North American and Europe. This suggests that lessons learned in this area may be directly applicable internationally.

Thrombocytopenia in Critically Ill Patients Receiving Thromboprophylaxis: Frequency, Risk Factors, and Outcomes

BACKGROUND Thrombocytopenia is the most common hemostatic disorder in critically ill patients. The objective of this study was to describe the incidence, risk factors, and outcomes of thrombocytopenia in patients admitted to medical-surgical ICUs. METHODS Three thousand seven hundred forty-six patients in 67 centers were enrolled in a randomized trial in which unfractionated heparin was compared with low-molecular-weight heparin (LMWH) for thromboprophylaxis. Patients who had baseline platelet counts < 75 × 10(9)/L or severe coagulopathy at screening were excluded. We analyzed the risk of developing mild (100-149 × 10(9)/L), moderate (50-99 × 10(9)/L), and severe (< 50 × 109/L) thrombocytopenia during an ICU stay. We also assessed independent and time-varying predictors of thrombocytopenia and the effect of thrombocytopenia on major bleeding, transfusions, and death. RESULTS The incidences of mild, moderate, and severe thrombocytopenia were 15.3%, 5.1%, and 1.6%, respectively. The predictors of each category of thrombocytopenia were APACHE (Acute Physiology and Chronic Health Evaluation) II score, use of inotropes or vasopressors, and renal replacement therapy. The risk of moderate thrombocytopenia was lower in patients who received LMWH thromboprophylaxis but higher in surgical patients and in patients who had liver disease. Each category of thrombocytopenia was associated with subsequent bleeding and transfusions. Moderate and severe thrombocytopenia were associated with increased ICU and hospital mortality. CONCLUSION A high severity of illness, prior surgery, use of inotropes or vasopressors, renal replacement therapy, and liver dysfunction are associated with a higher risk of thrombocytopenia developing in the ICU, whereas LMWH thromboprophylaxis is associated with a lower risk. Patients who develop thrombocytopenia in the ICU are more likely to bleed, receive transfusions, and die.

Helicobacter pylori infection in the Australian community: current prevalence and lack of association with ABO blood groups

Aims: To assess the current prevalence of Helicobacter pylori infection in an Australian urban population sample and to relate this to age, gender and ABO and Rhesus blood groups.

Plasma granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor levels in critical illness including sepsis and septic shock: relation to disease severity, multiple organ dysfunction, and mortality.

Objective To define the circulating levels of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) during critical illness and to determine their relationship to the severity of illness as measured by the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the development of multiple organ dysfunction, or mortality. Design Prospective cohort study. Setting University hospital intensive care unit. Patients A total of 82 critically ill adult patients in four clinically defined groups, namely septic shock (n = 29), sepsis without shock (n = 17), shock without sepsis (n = 22), and nonseptic, nonshock controls (n = 14). Interventions None. Measurements and Main Results During day 1 of septic shock, peak plasma levels of G-CSF, interleukin (IL)-6, and leukemia inhibitory factor (LIF), but not GM-CSF, were greater than in sepsis or shock alone (p < .001), and were correlated among themselves (rs = 0.44–0.77;p < .02) and with the APACHE II score (rs = 0.25–0.40;p = .03 to .18). G-CSF, IL-6, and LIF, and sepsis, shock, septic shock, and APACHE II scores were strongly associated with organ dysfunction or 5-day mortality by univariate analysis. However, multiple logistic regression analysis showed that only septic shock remained significantly associated with organ dysfunction and only APACHE II scores and shock with 5-day mortality. Similarly, peak G-CSF, IL-6, and LIF were poorly predictive of 30-day mortality. Conclusions Plasma levels of G-CSF, IL-6, and LIF are greatly elevated in critical illness, including septic shock, and are correlated with one another and with the severity of illness. However, they are not independently predictive of mortality, or the development of multiple organ dysfunction. GM-CSF was rarely elevated, suggesting different roles for G-CSF and GM-CSF in human septic shock.

Helicobacter pylori infection in intensive care: Increased prevalence and a new nosocomial infection

OBJECTIVE The pathogenesis of acute gastric stress ulceration in the seriously ill is uncertain, and any role of Helicobacter pylori infection is unknown. We aimed to assess the relationship between H. pylori serological status and stress ulceration in seriously ill patients, as well as H. pylori serological status in intensive care nurses as a marker for nosocomial infection. DESIGN Prospective epidemiologic survey. SETTING Adult intensive care unit in a university teaching hospital. PATIENTS One hundred patients, 100 nurses, and 500 blood donors as community controls. INTERVENTIONS H. pylori serological status was measured in patients, staff, and controls using a rapid whole blood test. Upper gastrointestinal bleeding and risk factors for acute stress ulceration were recorded. MEASUREMENTS AND MAIN RESULTS In seriously ill patients, H. pylori seropositivity (67%) was significantly higher than in the control group (39%) (p < .001). In patients, seropositivity was not related to age, country of birth, diagnostic category, severity of illness, or risk score for stress ulceration. There was a trend toward increased macroscopic gastric bleeding in seropositive patients. In intensive care nurses, H. pylori seropositivity (40%) was significantly higher than in age-matched controls (19%) (p < .001). Only duration of intensive care nursing was significantly associated with seropositivity (p = .02). CONCLUSIONS The unexpectedly high H. pylori seropositivity rate in this seriously ill cohort raises the possibility that under intensive care conditions, H. pylori infection may modulate responses to illness and injury, with consequent clinical implications. Furthermore, the elevated seropositivity rate in intensive care nurses suggests that H. pylori can be nosocomially transmitted.

Fatal Clostridium difficile infection of the small bowel after complex colorectal surgery

Pseudomembranous colitis is a well recognized complication of antibiotic use1 and is due to disturbances of the normal colonic bacterial flora, resulting in overgrowth of Clostridium difficile. For recurrent or severe cases, oral vancomycin or metronidazole is the treatment of choice. Progression to acute fulminant colitis with systemic toxic effects occasionally occurs, especially in the elderly and in the immunosuppressed. Some of these patients may need surgical intervention for complications such as perforation.2 Clostridium difficile is commonly regarded as a colonic pathogen and there are few reports of C. difficile enteritis with involvement of the small bowel (Table 1). Pseudomembrane formation caused by C. difficile is generally restricted to the colon, with abrupt termination at the ileocaecal valve.1,3,5,8,9 We report a case of fulminant and fatal C. difficile infection with pseudomembranes throughout the entire small bowel and colon in a patient following complex colorectal surgery. The relevant literature is reviewed.

An Adaptive Controller for Closed-Loop Management of Blood Pressure in Seriously Ill Patients

An adaptive control strategy is described which has been used for closed-loop computer control of blood pressure in patients in the Intensive Care and Cardiac Surgical Units of the Royal Melbourne Hospital. The initial development and testing of the control algorithm was done by simulation using computer facilities in the Intensive Care Unit. Adaptation to patient variability utilizes a model reference strategy. Control is based on readings of mean arterial pressure obtained from a standard patient monitor unit and implemented by controlling the infusion rate of a volumetric infusion pump. Patient data are displayed graphically on a VDU during control and stored on disk for subsequent postcontrol display and analysis by the medical staff. Clinical trials have indicated that the system is robust and can maintain effective control following sudden large variations in the patients blood pressure.