J Briegel, H Forst, M Haller, et al (Ludwig-Maximilians-Universitat Munchen, Munich)
Stress Doses of Hydrocortisone Reverse Hyperdynamic Septic Shock: A Prospective, Randomized, Double-blind, Single-center Study.
Crit Care Med 27:723-732, 1999.
Past studies have showed that stress doses of hydrocortisone were ineffective in septic shock. However, recent studies have shown that a patient in septic shock may have relative adrenocortical insufficiency.
In septic shock, a 100mg loading dose of hydrocortisone was given within 30 min, and followed by an infusion of (0.18mg/kg/hr) hydrocortisone. After reversal of shock, the dose was reduced to 0.08mg/kg/hr and continued for 6 days.
This significantly reduces the duration of vasopressor support and may shorten the time for resolution of sepsis induced organ dysfunction.
MB Malay, Jr Ashton RC, DW Landry, et al (Allegheny Gen Hosp, Pittsburgh, Pa; Columbia, Univ, New York)
Low-Dose Vasopressin in the Treatment of Vasodilatory Septic Shock
J Trauma 47: 699-705, 1999.
Refractory hypotension not responding to epinephrine in septic shock is potentially fatal. It has been suggested that vasopressin used concomitantly could give better results.
The vasopressor was infused at a rate of 0.04U/min. This permitted maintenance of arterial pressure thus allowing withdrawal of vasopressors.
MWA Angstwurm, J Schottdorf, J Schopohl, et la (Univ of Munich, Germany)
Selenium Replacement in Patients with Severe Systemic Inflammatory Response Syndrome Improves Clinical Outcome.
Crit Care Med 27: 1807-1813, 1999.
Systemic inflammatory response syndrome (SIRS) causes substantial morbidity and mortality. It has also been recorded that selenium concentrations are reduced in SIRS. This is a pilot study on the effects of selenium replacement on SIRS related morbidity and mortality.
Selenium was replaced as i.v. sodium selenite in a decreasing dosage over a period of 10 days.
Within 30 days, patients had normal selenium and glutathione peroxidose levels. There was significant reduction in Acute Physiologic and Chronic Health Evaluation III scores as compared to controls. Only 14% (as against 43% in controls) had renal failure and the mortality was 34% against 54% in the control group.
JE Gadek, and the Enteral Nutrition in ARDS Study Group (Ohio State Univ, Columbus; et al )
Effect of Enteral Feeding with Eicosapentaenoic Acid, g-Linolenic Acid, and Antioxidants in Patients with Acute Respiratory Distress Syndrome.
Crit Care Med 27: 1409-1420, 1999.
Low carbohydrate, high fat nutritional support for ventilated patients reduces demands on the respiratory system and decreases the severity of the inflammatory injury. Animal studies show that diets rich in eicosapentaenoic acid, g-linolenic acid and antioxidants can moderate inflammation. This is a prospective double blind randomized controlled trial (multi-centered) to evaluate the effect of a diet supplemented with EPA, GLA and antioxidants on the clinical outcome of ARDS.
The patients on the test diet required fewer days of ventilatory support in ICU or on supplemental oxygen and had less new organ failure. The infection rates were the same but the test diet patients had fewer adverse events.
VM Ranieri, PM Suter, C Tortorella, et al (Univ of Toronto)
Effect of Mechanical Ventilation on Inflammatory Mediators in Patients with Acute Respiratory Distress Syndrome: A Randomized Controlled Trial.
JAMA 282:54-61, 1999
Mechanical ventilation can escalate or cause an inflammatory response and acute lung injury. The influence of mechanical ventilation on the lung and systemic cytokine release was assessed in patients with ARDS.
Two groups were assessed (1) a control group and (2) a lung protective strategy group.
At baseline physiologic characteristics and cytokine concentrations were similar. But after 24 and 36 hours, there were significant between-group differences in tidal volume, end-inspiratory plateau pressures and PEEP. The lung protective strategy group had significantly better results. It could be concluded that mechanical ventilation can produce a cytokine response that may be diminished by minimising overdistension and recruitment and derecruitment of the lung.
PC Hebert, for the Canadian Critical Care Trials Group (Univ of Ottawa, Canada; et al)
A Multicenter, Randomized, Controlled Clinical Trial of Transfusion Requirements in Critical Care,
N Engl J Med 340: 409-417, 1999.
The optimal transfusion strategy for cirtically ill anaemia patients has not been standardised. A randomised, controlled study was undertaken comparing a restrictive (when Hb <7.0gms/dL) with a liberal approach (when Hb <10gms/dL).
The study was conducted on 838 critically ill patients randomly assigned to one of the two groups.
The overall 30 days mortality was similar. Mortality rates were significantly lower in the restrictive group in less acutely ill patients but was similar in critically ill patients. The mortality during hospitalization was significantly lower in the restrictive group.
S Deb, B Martin, L Sun, et al (Natl Naval Med Ctr, Bethesdam Md; Walter Reed Army Med Ctr, Washington, DC; Uniformed Services Univ of the Health Sciences, Bethesda, Md)
Resuscitation With Lactated Ringer’s Solution in Rats with Hemorrhagic Shock Induces Immediate Apoptosis.
J Trauma: Injury Infect Crit Care46: 582-589, 1999.
For patients in haemorrhagic shock, reperfusion injury can cause cell damage, leading to cell death and organ failure. Apoptotic cell death is thought to play an important role in the pathophysiology of haemorrhagic shock. The effects of resuscitation with lactated Ringer’s solution on cell apoptosis were assessed.
It was seen that the use of lactated Ringer’s solution for resuscitation caused a significant increase in cell apoptosis in the small intestine and the liver as compared with other agents used for resuscitation.
FA Luchette, BRH Robinson, LA Friend, et al (Univ of Cincinnati, Ohio)
Adrenergic Antagonists Reduce Lactic Acidosis in Response to Hemorrhagic Shock
J Trauma : Injury Infect Crit Care 46: 873-880, 1999.
a-blockers with a b-blocker significantly reduces plasma lactate levels, but had no effect on tissue perfusion. In an in-vitro study propranolol eliminated the increased lactate production by muscle in response to epinephrine.
The results question the use of lactate clearance as a resuscitation end point for patients with haemorrhagic shock.
E Barquist, E Fein, D Shadick, et al (Univ of Miami, Fla)
A Randomized Prospective Trial of Amphotericin B Lipid Emulsion Versus Dextrose Colloidal Solution in Critically ill Patients.
J Trauma 47: 336-340, 1999.
Amphotericin B is the drug of choice in fungal infections in critically ill patients. However, it carries at least a 50% risk of nephrotoxicity, inspite of preventive measures.
A trial was conducted using a combination of Amphotericin B with 20% intralipid solution in critically ill patients with positive fungal cultures of peritoneum, sputum or blood. The dose was 1mg/kg/d as against 0.5mg/kg/d given to controls (with 5% dextrose).
It was found to have less nephrotoxicity than Amphotericin with Dextrose. It can safely be given at a higher total cumulative dose.
RS Hotchkiss, PE Swanson, CM Knudson, et al (Washington Univ, St Louis)
Overexpression of Bcl-2 in Transgenic Mice Decreases Apoptosis and Improves Survival in Sepsis.
J Immunol 162: 4148-4156, 1999
Sepsis is associated with extensive lymphocyte apoptosis, which may reduce inflammation, but impairs host defences.
The effect of Bcl-2 (a protein product) has been shown to prevent apoptotic cell death. Its effect on lymphocyte apoptosis was studied in a rat model comparing 2 sets. (1) transgenic mice that selectively overexpressed B cl-2 in T lymphocytes as well as in endotoxin resistant species and (2) the endotoxin sensitive species.
The Bcl-2 overexpressors showed complete protection against sepsis induced apoptosis. The protective effect may result from the preservation of mitochondrial membrane potential preventing liver failure.
The aim of the study is to assess the influence of preoperative portal vein embolization on the long-term outcome of liver resection for colorectal metastases.
30 patients underwent PVE and 88 patients did not before resection of 4 or more liver segments. The groups were comparable in terms of sex, age, number and type of metastases (synchronous vs metachronous) and number of courses of neoadjuvant chemotherapy.
The main criterion for PVE was that resection was technically feasible but contraindicated because the remnant liver was too small (as estimated by CT scan volumetry). It was done when the estimated rate of remnant functional liver parenchyma (ERRFLP) was 40% or less.
PVE was feasible in all patients. There were no deaths with a complication rate of 3%. The post ERRFLP was significantly increased as compared to pre PVE value. Liver resection was performed in 19 patients (63%) with a mortality of 4% and complication rate of 7%. The survival rates after hepatectomy in both groups were comparable.
The authors conclude that PVE allows more patients with unresectable liver metastases to benefit from surgery.
Lena Gamrin, Pia Essen, Eric Hultman, et al (The Department of Anesthesiology and Intensive Care and Clinical Chemistry II, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden; and the Department of Surgery at State University of New York,Stony Brook, New York)
Protein-Sparing Effect in Skeletal Muscle of Growth Hormone Treatment in Critically III Patients.
Annals of Surgery, April 2000, 231(4), 577-586.
This study investigates the effect of growth hormone (GH) treatment on skeletal muscle protein catabolism in patients with multiple organ failure in the ICU.
20 critically ill ICU patients were randomized into 2 groups – one as control and the other with GH (0.3U/kg/day). Percutaneous muscle biopsy was taken before and 5 days after treatment starting on day 3 to 42 of the patient’s ICU stay. Protein content, protein synthesis, water nucleic acids and free amino acids were analysed.
The fractional protein synthesis rate and muscle free glutaminic increased in the GH group. Total intramuscular water did not increase but the intracellular water increased.
It is concluded that treatment with GH in patients with multiple organ failure, stimulated muscle protein synthesis, increased muscle free glutaminic and increased into a cellular water.
Byers RJ, Eddleston JM, Pearson RC, et al [Univ of Manchester, Manchester Royal Infirmary, England]
Dopexamine Reduces the Incidence of Acute Inflammation in the Gut Mucosa After Abdominal Surgery in High-risk Patients
Crit Care Med 27: 1787-1793, 1999
About 20% of critically ill patients have acute inflammation in the stomach/duodenum. Dopexamine has dopaminergic receptor agonist properties but no alpha or beta  effects. It may exhibit anti-inflammatory effects. Thus, a study was devised to examine endoscopically and histologically the effect of Dopexamine on gut mucosa. The study represented the side arm of a large, prospective, randomized, controlled, multicenter European Study [Effect of Dopexamine on Outcome after Major Abdominal Surgery].
38 patients with at least one high risk criterion, who were undergoing major abdominal surgery of at least 1.5 hours duration, were submitted to endoscopy and biopsy of the upper gastrointestinal tract immediately after anesthesia. After being stabilized, patients received placebo [Group A, n=12], 0.5 micro-g/Kg per minute of dopexamine [Group B, n=13], and 2.0 micro-g/kg per minute of dopexamine [ Group C, n=13]. At 72 hours, endoscopy and biopsy were repeated in 27 patients. Upper gut blood flow was estimated using tonometry. pH was calculated at baseline, after surgery, and 2,6,12,24,30 and 36 hours after surgery.
Gastric pH decreased significantly and similarly in all the three groups, with the greatest increase being recorded at the end of surgery. Erythema or hemorrhagic changes were found in 33.3% of Group A, 38.5% of Group B, and 15.4% of Group C. Erosive disease was seen in 25%, 7.7% and 38.5% respectively. At 72 hours, endoscopy revealed that the number of patients with no detectable abnormality had decreased to 25%, 20%, and 33.3% respectively. Polymorphonuclear neutrophil proliferation was seen in 86%, 37.5% and 37.5% respectively. There was no correlation between endoscopy and histologic findings.
Dopexamine does protect against the ill effects of decreased pH during surgery though it does not prevent such a decrease.
Hanson CW III, Deutschman CS, Anderson HL III, et al [Univ of Pennsylvania, Philadelphia : Univ of California, Irvine]
Effects of an Organized Critical Care Service on Outcomes and Resource Utilization : A Cohort Study
Crit Care Med 27: 270-274, 1999
Practice patterns are under scrutiny at both institutional and national levels to eliminate inefficiency, lower costs, and improve clinical results. Critical care medicine would seem to be particularly susceptible to the current forces of change. The cost and effectiveness of two patterns of critical care practice, in an academic medical center, were examined to determine whether presence of an on-site, organized, supervised critical care service improves care and reduces resource utilization.
Two patients cohorts admitted to a surgical intensive care unit [SICU] were compared. One group received care from an on-site critical care team, supervised by an intensive care specialist. The other group received care from a team with patient care responsibilities in multiple sites supervised by a general surgeon. The primary outcome measures were duration of stay, resource utilization, complication rates, resultant effects on added investigations, consultations, and terminal outcomes.
The results showed patients receiving care from an on-site critical care service had higher Acute Physiology and Chronic Health Evaluation II [APACHEII] scores, yet they spent less time in SICU, used fewer resources, had fewer complications, and had lower total hospital charges. These differences were more pronounced with increasing severity of illness.
Pronovest PJ, Jenckes MW, Dorman T, et al [John Hopkins Univ, Baltimore, MD]
Organizational Characteristics of Intensive Care Units Related to Outcomes of Abdominal Aortic Surgery
JAMA 281: 1310-1317, 1999
ICUs at different institutions vary widely in terms of morbidity and mortality rates. The effects of ICU structure and care processes on these outcomes are not known. The effects of ICU organization on the clinical and economic outcomes for patients undergoing abdominal aortic surgery were studied.
Hospital data on 2987 patients on whom abdominal aorta surgery was performed, in the state of Maryland, over a two year period, was analyzed. Data on organizational characteristics of ICUs were obtained from medical directors. The main outcomes assessed were in-hospital mortality, and length of total hospital and ICU stay.
The in-hospital mortality rates ranged from 0% to 66%. ICUs that did not have daily rounds by an ICU physician showed a 3-fold increase in in-hospital mortality after adjustment for patient demographic, co-morbidity, severity of illness, hospital and surgeon volume, and hospital characteristics. Other outcomes, such as cardiac arrest, acute renal failure, septicemia, and reintubation, were also more likely at centers without daily rounds by an ICU physician.
Leape LL, Cullen DJ, Clapp MD, et al [Harvard School of Public Health : Massachusetts Gen. Hospital; Brigham and Women’s Hosp., Boston]
Pharmacist Participation on Physicians Rounds and Adverse Drug Events in the Intensive Care Unit
JAMA 282: 267-270, 1999
Although studies show that pharmacist review of ICU prescription orders prevents mistakes and lowers drug costs by reducing drug use, there have been no studies on the benefits of having a pharmacist present in the ICU at the time drugs are prescribed. The efficacy of pharmacist participation in a medical ICU in preventing adverse drug events [ADEs] was tested in a controlled clinical trial.
Between February 1 and July 31, 1993 [Phase 1 Preintervention] and October 1, 1994 and July 7, 1995 [Phase 2 postintervention], the effect of pharmacist intervention was tested in a 17-bed ICU [the study unit] and compared with no pharmacist intervention in a 15-bed coronary care unit with similar occupancy rate [the control unit].
ADEs were compared for 75 randomly selected patients in each of the 3 groups from amongst all patients admitted to the study unit in Phase 1 and 2, and all patients admitted to the control unit in Phase 2. An experienced pharmacist made daily morning rounds with ICU personnel in the study unit; an experienced pharmacist was available for consultation but did not make daily rounds in the control unit. Outcome measures included measurements of ADEs, interventions the pharmacist made, and the acceptance of pharmacist interventions by the physicians and nurses.
The overall rate of preventable ordering and ADEs/1000 patient days decreased by 66% in the study unit from Phase 1 to 2, with significant savings in drugs costs. The rate of ADEs came down significantly in the study group from Phase 1 to 2. In the control group the rate of ADEs continued to remain high.
Of the 398 pharmacist interventions reported, 366 were related to ordering and 362 were accepted by the physicians. Pharmacist – initiated clarifications or correction of incomplete orders, wrong dose, wrong frequency, inappropriate choice, or duplicate therapy accounted for 46% of interventions. Drug interactions or adverse reactions were prevented in 22 cases.
The presence of a pharmacist at rounds in ICUs significantly reduces incidence of ADEs and result in substantial cost savings.
Darouiche RO for the Catheter Study Group [Baylor College of Medicine, Houston, et al]
A Comparison of Two Antimicrobial -Impregnated Central Venous Catheters
N. Engl J Med 340: 1-8, 1999
Previous studies have shown that rates of central venous catheter colonization and catheter related blood stream infection can be significantly reduced through the use of catheters impregnated with minocycline and rifamycin or with chlorhexidine and silver sulphadiazine. However, no studies have directly compared the benefits of the two types of catheter. Minocycline/rifamycin and chlorhexidine/silver sulphadiazine catheters were compared for their ability to prevent colonization and catheter-related blood stream infections.
The prospective, multicenter trial included adult patients considered at high risk for catheter-related infection who were likely to require a central venous catheter for 3 days or longer. The patients were randomized to receive polyurethane triple-lumen catheters impregnated with minocycline/rifamycin on the luminal and external surfaces or with chlorhexidine/silver sulphadiazine on the external surface only. Catheter tips and subcutaneous segments were cultured by both the roll-plate and sonication methods after removal, with peripheral blood cultures performed as indicated. The analyses included a total of 738 catheters with evaluable culture results.
The two catheter groups were similar in their clinical characteristics and infection risk factors. The catheter colonization rate was 8.3% with monocycline/rifamycin impregnated catheters vs 22.8% in the other group. The former were also associated with lower rate of blood stream infection [0.3% vs 3.4%]. The authors emphasize that adequate aseptic technique must complement the use of monocycline/rifamycin impregnation of central venous catheters.
Arons MM, for the Ibuprofen in Sepsis Study group [Vanderbilt Univ., Nashville, Tenn]
Effects of Ibuprofen on the Physiology and Survival of Hypothermic Sepsis
Crit Care Med 27:699-707, 1999
Patients whose response to sepsis is hypothermic rather than febrile have a poor prognosis. It has been suggested that patients with hypothermic sepsis represent a clinically and biochemically distinct subgroup. This hypothesis was studied, along with the response to ibuprofen treatment in patients with hypothermic sepsis.
The multicenter trial included 455 patients admitted to the ICU with severe sepsis and a known or suspected serious infection. Patients with hypothermic sepsis were identified, and their clinical and physiologic findings were compared with those of patients with febrile sepsis. Plasma cytokines measured included tumor necrosis factor [TNF – alpha] and interleukin [IL]-6, along with the lipid mediators thromboxane B2[TxB], and prostacyclin. Hypothermic patients were randomized to receive ibuprofen [10 mg/kg IV over 30 to 60 minutes every 6 hours for 8 doses, to a maximum of 800 gm] or to receive a placebo.
Ten percent of all patients with sepsis were hypothermic, with a temperature below 35.5 degrees celsius. The mortality rate was double in these patients compared to the rest [70% vs 35%], and they had significant baseline elevations of urinary TxB, metabolites, prostacyclin, and serum TNF-alpha and IL-6, compared with the febrile group.
About ten percent of the patients with sepsis have hypothermia instead of a febrile response. Such patients have an increased mortality. Treatment with ibuprofen may reduce mortality, but prospective confirmation of these findings is needed.
Goldhaber SZ [Harvard Med school]
N. Engl J Med 339 : 93-104, 1998
The best approach to diagnosis of pulmonary embolism is a careful history and physical examination with selective testing as indicated.
Current understanding of the importance of the right ventricular dysfunction enables more accurate prognosis in patients with pulmonary embolism. Finally, the take home message is that surgeons should have a low threshold to evaluate seemingly minor post operative complications viz, fever, tachycardia because many of these patients have small pulmonary embolism that are effectively treated by aggressive anticoagulation.
Heyland DK, for the Canadian Critical Care Trials Group [Queens Univ, Kingston, Ont, Canada; et al]
The Clinical Utility of Invasive Diagnostic Techniques in the Setting of Ventilator – Associated Pneumonia
Chest 115: 1076-1084, 1999
Ventricular-associated pneumonia [VAP] is often diagnosed on clinical grounds alone and contributes to the morbidity, mortality and costs of caring for critically ill patients. Overdiagnosis may be disastrous with the use of needless antibiotics and the delay in recognition of the true diagnosis.
The utility of invasive investigations like bronchoscopy, with protected brush catheter [PBC] bronchoalveolar lavage [BAL] was evaluated in 92 patients receiving ventilatory support with a clinical suspicion of VAP.
The results showed that VAP was often overdiagnosed after BAL or PBC after these procedures. Patients received fewer antibiotics. Both groups had similar duration of mechanical ventilation and ICU stay. Those who underwent PBC/BAL had a lower mortality.
Invasive diagnostic testing may boost physicians confidence in the diagnosis and management of VAP.