快樂小藥師 Im pharmacist nichts glücklich

接著上一次的文章，這次是第2～第6

Acute renal failure, In patients with chronic renal insufficiency undergoing cardiac surgery; Prophylaxis

1) Overview

FDA Approval: Adult, no; Pediatric, no Efficacy: Adult, Evidence is inconclusive

Recommendation: Adult, Class IIb

Strength of Evidence: Adult, Category B

2) Summary:

In a randomized, placebo-controlled, prospective study (n=254) of patients with chronic renal insufficiency undergoing cardiac surgery, intravenous administration of N-acetylcysteine (NAC) reduced the incidence of acute renal failure (ARF) compared to placebo, but the results did not reach statistical significance (40% versus 52%; p=0.06) (Sisillo et al, 2008).

3) Adult:

a) In a randomized, placebo-controlled, prospective study (n=254), of patients with chronic renal insufficiency undergoing cardiac surgery, intravenous administration of N-acetylcysteine (NAC) reduced the incidence of acute renal failure (ARF) compared to placebo, but the results did not reach statistical significance (40% versus 52%; p=0.06). Patients with chronic renal insufficiency (estimated creatinine clearance less than or equal to 60 milliliters/minute) were randomized to receive intravenous NAC 1200 milligrams every 12 hours for four doses starting immediately before cardiac surgery (n=129), or placebo (n=125). The primary study outcome was the incidence of ARF (greater than 25% increase in serum creatinine from baseline to the maximum value obtained within 72 hours following cardiac surgery). Creatinine measurements were obtained the day before surgery, and every day following surgery until discharge. Secondary outcomes studied were the maximal change in calculated creatinine clearance, doubling of serum creatinine according to the RIFLE (Risk of renal dysfunction, Injury to the kidney, Failure of kidney function, Loss of kidney function, and End-stage kidney disease) definition for acute kidney injury, and the incidence of major postoperative clinical events, including the requirement for renal replacement therapy, acute myocardial infarction, prolonged (greater than 48 hours) mechanical ventilation, prolonged (greater than 4 days) intensive care unit stay, and death. ARF occurred in 118 (46%) of the total study group and 16 (6%) of patients required renal replacement therapy. The incidence of ARF was 40% (n=52) in the NAC group versus 52% (n=65) in the placebo group (p=0.06)(relative risk (RR) 1.6 (95% confidence interval (CI) 0.98 to 2.63; p=0.06). The maximal creatinine increase versus baseline was a mean value of 34+/- 44% in the NAC group and 39+/- 50% for the placebo group (p=0.39). In the NAC group, there was a lower incidence of prolonged mechanical ventilation (3% versus 18%; RR 6.67; 95% CI 2.32 to 19.08; p less than 0.001) and prolonged ICU stay (13% versus 33%; RR 3.22; 95% CI 1.72 to 6.01; p less than 0.001). A significant benefit, in terms of ARF incidence was noted in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB)(40% of ARF in NAC treated patients versus 54% in placebo-treated patients; p=0.03). No significant benefit was noted in patients who did not require CPB (46% of ARF in NAC patients versus 31% in placebo-treated patients; p=0.41). Overall mortality, 4 (3%) patients died in the control group and 5 (4%) patients died in the NAC group (p=0.77) (Sisillo et al, 2008)

Acute respiratory distress syndrome

1) Overview

FDA Approval: Adult, no; Pediatric, no

Efficacy: Adult, Evidence is inconclusive

Recommendation: Adult, Class IIb

Strength of Evidence: Adult, Category B

2) Summary:

Acetylcysteine had beneficial effects in patients with adult respiratory distress syndrome (ARDS) (Bernard et al, 1997).

3) Adult:

a) Repletion of glutathione by administration of acetylcysteine to patients with adult respiratory distress syndrome (ARDS) may reduce the duration of lung injury. In a randomized, double-blind study of patients with ARDS of various etiologies, 14 patients received N-acetylcysteine (NAC) 70 milligrams/kilogram body weight (mg/kg), 17 received another cysteine precursor (L-2-oxothiazolidine-4-carboxylate, OTZ) 63 mg/kg, and 15 received placebo, intravenously every 8 hours for 10 days. Red blood cell glutathione increased significantly in the NAC group (p less than 0.05) during the 10 days. Of the patients receiving NAC or OTZ, 39% developed a new organ failure during treatment, while 73% of the placebo group developed a new organ failure (p=0.057). Mortality after 30 days of follow-up was not different among groups (Bernard et al, 1997).
b) Acetylcysteine was administered to a patient with adult respiratory distress syndrome and renal failure as a complication of acute pancreatitis (Braganza et al, 1986). Acetylcysteine was given at half the dosage recommended for acetaminophen poisoning and given over 56 hours. The precise dose and route were not specified in this report, although the intravenous route was implied. Within 72 hours of the start of acetylcysteine, inotropic and renal support were no longer needed, and the need for oxygen was reduced from 100% to 50%.

Administration of anesthesia for procedure

FDA Labeled Indication
1) Overview

FDA Approval: Adult, yes; Pediatric, yes

Efficacy: Adult, Effective; Pediatric, Effective

Recommendation: Adult, Class IIa; Pediatric, Class IIa

Strength of Evidence: Adult, Category B; Pediatric, Category B

2) Summary:

Acetylcysteine inhalation solution is indicated as adjuvant therapy for patients with abnormal, viscid, or inspissated mucous secretions including use during anesthesia (Prod Info acetylcysteine inhalation solution, 2004).

Asthmatic bronchitis, chronic

FDA Labeled Indication
1) Overview

FDA Approval: Adult, yes; Pediatric, yes

Efficacy: Adult, Effective; Pediatric, Effective

Recommendation: Adult, Class IIa; Pediatric, Class IIa

Strength of Evidence: Adult, Category B; Pediatric, Category B

2) Summary:

Acetylcysteine inhalation solution is indicated as an adjuvant therapy for patients with abnormal, viscid, or inspissated mucous secretions in several conditions including chronic asthmatic bronchitis (Prod Info acetylcysteine inhalation solution, 2004).
A meta-analysis of published studies examining the effects of N-acetylcysteine (NAC) on chronic bronchitis concluded that oral NAC is more efficacious and no more harmful than placebo for treating bronchitis (Stey et al, 2000).
A meta-analysis of randomized, double-blind, placebo-controlled trials (n=8) studying the effect of long-term oral acetylcysteine on prevention of acute exacerbations of chronic bronchitis showed a beneficial effect of acetylcysteine, relative to placebo (Grandjean et al, 2000).
Chronic bronchitis patients taking acetylcysteine showed a significant reduction in the number of days during which they were incapacitated (Parr & Huitson, 1987).

3) Adult:

a) A meta-analysis of published studies examining the effects of N-acetylcysteine (NAC) on chronic bronchitis concluded that oral NAC is more efficacious and no more harmful than placebo for treating bronchitis. Eleven trials met inclusion criteria, including having a placebo control group, adequate randomization and blinding, and description of withdrawals. When data from all studies reporting exacerbations (n=9) were combined, the difference between NAC and placebo treatments was statistically significant (relative benefit=1.56, 95% confidence interval, 1.37-1.77). The number needed to treat to prevent an exacerbation in 1 person was 5.8. Patient assessment of efficacy was superior with NAC compared to placebo, with the number-needed-to-treat for one patient reporting improvement compared to placebo being 3.7. Adverse effects were no more common with NAC than with placebo. The clinical relevance of the benefit of NAC remains to be established (Stey et al, 2000).
b) A meta-analysis of randomized, double-blind, placebo- controlled trials (n=8) studying the effect of long-term oral acetylcysteine on prevention of acute exacerbations of chronic bronchitis showed a beneficial effect of acetylcysteine, relative to placebo. Dosages of acetylcysteine ranged from 600 milligrams (mg) 3 times per week to 1200 mg/day. Although statistical significance was not attained in any individual trial, meta- analysis showed the weighted average reduction in the number of acute exacerbations with acetylcysteine treatment to be 23% (95% confidence interval: -12% to -33%). Although this reduction is not dramatic, it may significantly decrease morbidity and health care costs (Grandjean et al, 2000).
c) Chronic bronchitis patients taking acetylcysteine showed a significant reduction in the number of days during which they were incapacitated. Overall, 526 patients suffering from chronic bronchitis were randomized to receive either acetylcysteine 200 milligrams 3 times a day or placebo during a 6-month period. The authors failed to find any statistically significant difference in the number of acute exacerbations between the 2 treatment groups, although there was a slight trend toward improvement in the acetylcysteine group during the first 3 months of the trial. The tolerability was similar for both treatments (Parr & Huitson, 1987).
d) N-acetylcysteine 200 milligrams 3 times a day (sachets) was more effective than placebo in improving difficulty in expectoration and cough severity in chronic bronchitis patients in a controlled study (Jackson et al, 1984). Toxicity was minimal.
e) The results of a general practice study of 1686 patients suggest that acetylcysteine administered orally (200 milligrams three times daily for 2 months) to patients with chronic bronchitis effectively changes the viscosity and character of sputum with resultant ease of expectoration and cough severity. There was a notable improvement in associated abnormal physical signs such as the presence of rhonchi, crepitations, and dyspnea at rest. Tolerability was good, with 81% of patients experiencing no side effects; gastrointestinal effects (ie, nausea and vomiting) were most frequent (Tattersall et al, 1983).

Atelectasis, Due to mucous obstruction

FDA Labeled Indication
1) Overview

FDA Approval: Adult, yes; Pediatric, yes

Efficacy: Adult, Evidence favors efficacy; Pediatric, Evidence favors efficacy

Recommendation: Adult, Class IIb; Pediatric, Class IIb

Strength of Evidence: Adult, Category B; Pediatric, Category B

2) Summary:

Acetylcysteine inhalation solution is indicated as adjuvant therapy for patients with abnormal, viscid, or inspissated mucous secretions in several conditions including atelectasis due to mucous obstruction (Prod Info acetylcysteine inhalation solution, 2004).

3) Adult:

a) Two reports describe the use of acetylcysteine (NAC) in preventing postoperative atelectasis with conflicting results. The first report was based on a randomized non-blinded study of NAC and saline in post-thoracic and abdominal surgery patients (Thomas et al, 1966). To obtain baseline control values, the group was evaluated prior to beginning the active drug study. The authors reported half as many cases of atelectasis with NAC, but were unable to substantiate these findings in a subsequent report of post-thoracotomy patients (Thomas et al, 1967).