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N-acetylcysteine raises blood loss risk in cardiac surgery

Patients with moderate renal insufficiency who undergo cardiac surgery are at risk for blood loss and increased need for blood product transfusion if they're given N-acetylcysteine to prevent perioperative inflammation and ischemia-reperfusion injury, according to a study.


Researchers studied the effects of N-acetylcysteine in 177 patients randomized to two groups. The study group received an I.V. infusion of N-acetylcysteine until 4 hours after cardiopulmonary bypass; the control group received a placebo. All patients had preexisting moderate renal insufficiency, with an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2.


The researchers evaluated hemostasis by comparing the two groups' hemoglobin, platelet, and coagulation values; chest-tube blood loss, and need for blood product transfusion. The patients who received N-acetylcysteine had a mean 24-hour chest-tube blood loss that was 261 mL higher than the control group, and were transfused 1.6 more units of red blood cells during hospitalization, compared to the control group.


Further research is needed to determine how N-acetylcysteine impairs hemostasis, and to determine when the risks of bleeding outweigh the drug's benefit for perioperative organ protection. In the meantime, clinicians should consider the potential for impaired hemostasis when using N-acetylcysteine in the perioperative setting, and should monitor patients carefully when using this drug.


Source: Wijeysundera DN, Karkouti K, Rao V, et al. N-acetylcysteine is associated with increased blood loss and blood product utilization during cardiac surgery. Crit Care Med. 2009;37(6):1929-1934.


Acid-suppressing drugs increase risk of pneumonia

Hospitalized patients who are taking acid-suppressive medication are at 30% greater risk of contracting healthcare-associated pneumonia, according to a recent study.


According to the researchers, acid-suppressive therapy isn't supported by the literature in up to 70% of hospitalized patients taking these medications (for example, stress ulcer prophylaxis in low-risk patients). Over three years, the researchers studied nearly 64,000 adult patients who were hospitalized for at least 3 days, and for a variety of conditions. (Patients admitted to the ICU were excluded.)


Acid-suppressive medications were ordered for 52% of the patients in the study, and 3.5% of the study patients developed healthcare-associated pneumonia. The unadjusted incidence of healthcare-associated pneumonia in the acid-suppressive group was 4.9%, compared to 2% in the group that wasn't on this therapy. Proton-pump inhibitors were more likely to be associated with healthcare-associated pneumonia than histamine2 receptor antagonists.


The study concluded that acid-suppressive therapy increased the risk of healthcare-associated pneumonia 30% in nonventilated hospitalized patients. More research is needed, the study authors said, to determine appropriate use of these medications in hospitalized patients.


Source: Herzig SJ, Howell MD, Ngo LH, Marcantonio ER. Acid-suppressive medication use and the risk for hospital-acquired pneumonia. JAMA. 2009;301(20):2120-2128.


Increasing norepinephrine doses may help in septic shock

Increasing norepinephrine doses to raise the mean arterial pressure (MAP) of patients with septic shock increases tissue oxygenation, improving hemodynamics without exacerbating abnormalities in microcirculatory flow, according to a study.


Sepsis is characterized by vasodilation, hypovolemia, myocardial depression, and altered microvascular flow. Patients with septic shock have arterial hypotension (a MAP of less than 60 mm Hg) despite aggressive fluid resuscitation.


Researchers followed 16 patients with septic shock, increasing the norepinephrine dose to increase the patients' MAPs from 60 mm Hg to 70, then 80, and finally 90 mm Hg. The patients' hemodynamic statuses were monitored, and sidestream darkfield imaging was used to determine the sublingual microvascular flow index and proportion of perfused vessels.


Although further research is needed to determine the optimal role of vasopressors in patients with septic shock, increasing norepinephrine dosages to raise MAP increases global oxygen delivery, cutaneous microvascular flow, and tissue oxygenation, the researchers said.


Source: Jhanji S, Stirling S, Patel N, Hinds CJ, Pearse RM. The effect of increasing doses of norepinephrine on tissue oxygenation and microvascular flow in patients with septic shock. Crit Care Med. 2009;37(6):1961-1966.


Some ICU patients may benefit from early antifungal therapy

Invasive candidiasis is associated with significant morbidity and mortality in critically ill patients, but can be difficult to recognize. This study reviewed the use of early antifungal therapy and found that it should be limited to patients at high risk for invasive candidiasis.


The researchers reviewed all relevant peer-reviewed original articles, meta-analyses, guidelines, consensus statements, and review articles from 1966 to July 2008 on early antifungal therapy.


Risk factors for invasive candidiasis include colonization, antibiotic use, surgery, central venous catheter or indwelling urinary catheter use, renal failure and dialysis, parenteral nutrition, diabetes, mechanical ventilation, length of ICU stay, and profound neutropenia.


Widespread use of antifungals isn't recommended by the researchers, because of the risk of increased resistance. Although early antifungal therapy in high-risk patients can reduce the incidence of invasive candidiasis, the study didn't find that it increased patients' survival rates. As a result, the researchers recommend that clinicians assess patients on a case-by-case basis and determine the need for early antifungal treatment strategies based on frequent evaluations of risk factors and clinical status.


Source: Lam SW, Eschenauer GA, Carver PL. Evolving role of early antifungals in the adult intensive care unit. Crit Care Med. 2009;37(5):1580-1593.


Rivastigmine may not prevent postoperative delirium in older cardiac surgery patients

Patients who've had cardiac surgery frequently develop postoperative delirium, which is associated with increased 1-year mortality, late cognitive deficits, and higher costs. No drugs have been recommended to prevent this delirium, which may be caused by impaired cholinergic transmission.


In this study, researchers studied 120 patients who had elective cardiac surgery with cardiopulmonary bypass. The patients, all age 65 or older, were randomized to receive either placebo or 1.5 mg of oral rivastigmine (a cholinesterase inhibitor) three times per day. Patients in the rivastigmine group took the medication the evening before surgery and continued through the evening of the sixth postoperative day.


Delirium, diagnosed with the Confusion Assessment Method within 6 days postoperatively, developed in 30% of the placebo group and 32% of the rivastigmine group. Patients with delirium were treated with haloperidol and lorazepam.


This negative or, because of methodologic issues, possibly failed trial doesn't support short-term prophylactic administration of oral rivastigmine to prevent postoperative delirium in older patients undergoing elective cardiac surgery with cardiopulmonary bypass.


Source: Gamberini M, Bollinger D, Lurati Buse GA, et al. Rivastigmine for the prevention of postoperative delirium in elderly patients undergoing elective cardiac surgery-a randomized controlled trial. Crit Care Med. 2009;37(5):1762-1768.


Low-dose corticosteroids can help in ALI and ARDS

Although still controversial, the use of low-dose corticosteroids to reduce mortality and morbidity of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), without increasing the risk of adverse reactions, appears to be supported by a recent meta-analysis.


Researchers reviewed all randomized controlled studies and observational studies on prolonged low-to-moderate-dose corticosteroid therapy for ALI or ARDS. They found that the studies showed a similar trend toward reduced mortality, improved length of ventilator-free days, reduced length of ICU stay, and improved PaO2/FIO2 ratio. No increases were found in infection, neuromyopathy, or other major complications.


The researchers concluded that the consistency of results in both study designs and all outcomes suggests that low-dose corticosteroids are an effective treatment for ALI or ARDS. However, the mortality benefits of this therapy in patients with early ARDS should be confirmed by an adequately powered randomized trial.


Source: Tang BMP, Craig JC, Eslick GD, Seppelt I, McLean AS. Use of corticosteroids in acute lung injury and acute respiratory distress syndrome: a systematic review and meta-analysis. Crit Care Med. 2009;37(5):1594-1603.