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[Micromedex][01] acetylcysteine 適應症整理

[Micromedex][02]Acetylcysteine適應症整理

[Micromedex][03]Acetylcysteine適應症整理

[Micromedex][04]Acetylcysteine 適應症整理

第22～3522

HIV infection 人類免疫不全病毒感染

1) Overview

FDA Approval: Adult, no; Pediatric, no

Efficacy: Adult, Ineffective

Recommendation: Adult, Class III

Strength of Evidence: Adult, Category B

2) Summary:

N-acetylcysteine (NAC) may decrease tumor necrosis factor levels and activated suppressor cells (Akerlund et al, 1996; Look et al, 1998).
Treatment of symptom-free HIV (human immunodeficiency virus)-infected patients with acetylcysteine (AC) and selenium resulted in beneficial changes in lymphocyte subsets but did not affect plasma glutathione (GSH) or the balance of oxidized and reduced GSH (Look et al, 1998).

3) Adult:

a) When N-acetylcysteine (NAC) was tested in HIV-patients, it was found to increase plasma concentrations of cysteine but not to inhibit free-radical production by neutrophils; CD4+ cell loss continued, but the rate of loss might have been slowed (Akerlund et al, 1996). The double-blind, placebo-controlled study was completed in 37 asymptomatic HIV-seropositive volunteers, who were randomized to receive acetylcysteine (800 mg per day in 2 divided doses) or placebo for 4 months. Pretreatment effects showed that HIV-seropositive participants had lower plasma cysteine concentrations, higher TNF-alpha levels, and higher free radical activity in neutrophils in plasma than did non-HIV-seropositive controls; no significant differences were found in glutathione plasma levels. At the end of the study, the NAC group had significantly higher plasma cysteine levels (p=0.005) and lower TNF-alpha levels (p less than 0.05) compared with the placebo group, but no difference was observed in plasma-induced radical production by neutrophils. Two people did not complete the study because of side effects.
b) Treatment of symptom-free HIV (human immunodeficiency virus)-infected patients with acetylcysteine (AC) and selenium resulted in beneficial changes in lymphocyte subsets but did not affect plasma glutathione (GSH) or the balance of oxidized and reduced GSH. In a randomized, partial crossover trial, 13 patients were given AC 1800 milligrams/day and sodium selenite 500 micrograms/day for 24 weeks (group A). Another similar 11 patients were given no treatment for 12 weeks and the active treatment for the next 12 weeks (group B). At 6 and 12 weeks, group A showed a significantly reduced CD4 lymphocyte percentage, CD8 lymphocyte count, and percentage of activated suppressor cells (CD8/CD38) relative to group B. Although there was no increase in CD4 lymphocyte count, the ratio of CD4 to CD8 lymphocytes rose. These changes were regarded as a beneficial treatment effect. Baseline levels of GSH in the HIV-infected patients were lower than in healthy controls. The absence of change in plasma GSH concentration over 24 weeks of treatment suggests that low cysteine availability is not the cause of the GSH depletion in HIV-infected patients. Because baseline and 12-week measures of viral load were so near the limit of detection, the absence of change cannot be interpreted (Look et al, 1998).

23

Injury of lung 肺損傷

1) Overview

FDA Approval: Adult, no; Pediatric, no

Efficacy: Pediatric, Evidence is inconclusive

Recommendation: Pediatric, Class IIb

Strength of Evidence: Pediatric, Category B

2) Summary:

Progressive pulmonary failure and mortality were reduced in children who received aerosolized heparin and acetylcysteine in addition to standard treatment for burns and smoke inhalation compared to children who received standard therapy alone (Desai et al, 1998).

3) Pediatric:

a) Progressive pulmonary failure and mortality were reduced in children who received aerosolized heparin and acetylcysteine in addition to standard treatment for burns and smoke inhalation compared to children who received standard therapy alone. Forty-seven children with bronchoscopically identified inhalation injury and needing mechanical ventilation received aerosolized heparin 5000 units, alternating with 3 milliliters of a 20% solution of acetylcysteine, every 2 hours for the first 7 days after injury. Another 43 similar children served as controls. The incidences of reintubation for progressive pulmonary failure, atelectasis and mortality were all significantly lower in the treatment group than in the control group (p less than 0.05) (Desai et al, 1998).

24

Lamellar ichthyosis 層狀魚鱗癬

1) Overview

FDA Approval: Adult, no; Pediatric, no

Efficacy: Adult, Evidence is inconclusive

Recommendation: Adult, Class IIb

Strength of Evidence: Adult, Category C

2) Summary:

Topical application of a water-in-oil emulsion containing 10% N-acetylcysteine (NAC) significantly improved lamellar ichthyosis in one case report (Redondo & Bauza, 1999).

3) Adult:

a) Topical application of a water-in-oil emulsion containing 10% N-acetylcysteine (NAC) significantly improved lamellar ichthyosis in a 33-year-old woman who had been treated for 2 years with acitretin 30 milligrams per day and urea lotions. The NAC-containing emulsion was applied to one forearm and the vehicle to the other forearm. Outstanding improvement was evident at 5 weeks on the NAC-treated arm, whereas there was no change in placebo-treated areas. A culture of keratinocytes showed that NAC inhibited cell growth in a dose- and time-dependent manner (Redondo & Bauza, 1999).

25

Malaria 瘧疾

1) Overview

FDA Approval: Adult, no; Pediatric, no

Efficacy: Adult, Evidence favors efficacy

Recommendation: Adult, Class IIb

Strength of Evidence: Adult, Category B

2) Summary:

Serum lactate levels in subjects with severe malaria returned to normal twice as quickly after N-acetylcysteine (NAC) administration compared to placebo in a double-blind prospective study (n=30) (Watt et al, 2002).

3) Adult:

a) Serum lactate levels in subjects with severe malaria returned to normal twice as quickly after N-acetylcysteine (NAC) administration compared to placebo in a double-blind prospective study. Adult males (18 to 50 years, n=30) with severe malaria being treated with quinine were administered either 300 milligrams/kilogram (mg/kg) NAC or placebo for 20 hours. Over 15 minutes, a NAC loading dose (150 mg/kg) was intravenously infused in 200 milliliters (mL) of 5% dextrose. This was followed by a 4-hour infusion of NAC 50 mg/kg in 500 mL of 5% dextrose. Over the next 16 hours, 100 mg/kg in one liter of 5% dextrose was infused. Placebo was 5% dextrose. In NAC-treated subjects, lactate concentrations were restored to normal twice as quickly (median=21 hours, 95% confidence interval 12 to 36 hours) compared to placebo subjects (median=42 hours, 95% confidence interval 30 to 84 hours; p=0.002). In severe malaria, elevated blood lactate is a significant prognosticator of outcome (Watt et al, 2002).

26

Meconium ileus 胎糞性腸阻塞

1) Overview

FDA Approval: Adult, no; Pediatric, no

Efficacy: Adult, Evidence is inconclusive; Pediatric, Evidence is inconclusive

Recommendation: Adult, Class IIb; Pediatric, Class IIb

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

2) Summary:

Acetylcysteine enemas have been effective in removing meconium plugs (Spiro, 1977; Hodson et al, 1976; Derman et al, 1975).

3) Adult:

a) The use of acetylcysteine enemas has been reported in connection with meconium ileus, meconium plugs, and meconium ileus equivalent (Spiro, 1977). Meconium ileus equivalent describes intestinal obstruction in cystic fibrosis patients outside the neonatal period (Spiro, 1977; Hodson et al, 1976). Some adults with cystic fibrosis and meconium ileus equivalent have been successfully treated with acetylcysteine enemas (Hodson et al, 1976).

4) Pediatric:

a) Meconium ileus and plugs, generally seen in newborn infants, are characterized by bowel obstruction caused by inspissated, protein-rich, tenacious meconium (Spiro, 1977; Shirkey, 1975; Kopel, 1972). Meconium ileus is present in about 10% to 20% of infants with cystic fibrosis, while meconium plugs are not related to the disease (Spiro, 1977; Kopel, 1972).
b) One report described the successful treatment of a neonate with acetylcysteine enemas (Simpson et al, 1968). A 10% acetylcysteine solution (20% acetylcysteine, 30 milliliters; normal saline, 30 milliliters) was administered as an enema and the buttocks were held together manually for five minutes. A few minutes later a 10-cm ribbon of meconium was passed. The procedure was repeated four times within 14 hours, with good results. At that time 20 milliliters of the 10% solution was given via nasogastric tube passed into the upper jejunum; six hours later a huge stool was passed, clearing the bowel.
c) A 9-year-old girl with cystic fibrosis and meconium ileus equivalent was treated successfully with 4% acetylcysteine enemas (diluted to 300 milliliters with normal saline) at twelve-hour intervals (five enemas total) (Derman et al, 1975).

27

Multiple organ failure; Prophylaxis 預防多重器官衰竭

1) Overview

FDA Approval: Adult, no; Pediatric, no

Efficacy: Adult, Evidence is inconclusive

Recommendation: Adult, Class III

Strength of Evidence: Adult, Category B

2) Summary:

Mortality was not decreased by infusion of N-acetylcysteine (NAC) into critically ill, mechanically ventilated patients who required support of two or more major organ systems or who had moderate or severe organ failure of one system (Molnar et al, 1999).

3) Adult:

a) Mortality was not decreased by infusion of N-acetylcysteine (NAC) into critically ill, mechanically ventilated patients who required support of two or more major organ systems or who had moderate or severe organ failure of one system. Upon admission to the intensive care unit (ICU), patients fulfilling study criteria were randomly assigned to receive NAC as a bolus of 150 milligrams/kilogram (mg/kg) in 250 milliliters (mL) of 5% dextrose, followed by a continuous infusion of 12 mg/kg/hour in 500 mL of 5% dextrose per 24 hours (n=41), or 5% dextrose (placebo; n=45). Treatment continued for a minimum of 3 days and a maximum of 5 days, depending on multiple organ dysfunction scores. Liver function was significantly improved in NAC-treated patients (p=0.01), but the function of no other organ system was improved by NAC. Among patients admitted to the ICU more than 24 hours after hospital admission, mortality in the NAC group was nearly twice that in the placebo group, suggesting that NAC at the time and doses given may actually have had harmful effects (Molnar et al, 1999).

28

Occlusion of ureter, Mucolysis  輸尿管阻塞

1) Overview

FDA Approval: Adult, no; Pediatric, no

Efficacy: Adult, Evidence is inconclusive

Recommendation: Adult, Class IIb

Strength of Evidence: Adult, Category C

2) Summary:

In one case report, acetylcysteine was effectively used for relief of mucinous obstruction of the distal ureter after a mid-ureteral replacement with ileum (Benderev, 1988).

3) Adult:

a) Acetylcysteine was effectively used for relief of mucinous obstruction of the distal ureter after a mid-ureteral replacement with ileum. Acetylcysteine (300 milliliters of 1% solution) was instilled at low pressure via nephrostomy tube following documentation of the obstruction with a nephrostogram. Patency of the ureter was achieved within 5 minutes. Re-obstruction ensued but it resolved with repeat percutaneous instillation of acetylcysteine. Patency, confirmed by a follow-up nuclear renogram at 4 months, was maintained with 700 milligrams acetylcysteine orally 4 times a day (Benderev, 1988).

29

Operation on heart 心臟手術

1) Overview

FDA Approval: Adult, no; Pediatric, no

Efficacy: Adult, Evidence is inconclusive

Recommendation: Adult, Class III

Strength of Evidence: Adult, Category C

2) Summary:

Pre-operative acetylcysteine (NAC) may be useful in maintaining respiratory function and downregulating immune system responses to cardiopulmonary surgery and extracorporeal circulation (De Backer et al, 1996).

3) Adult:

a) Pre-operative acetylcysteine (NAC) may be useful in maintaining respiratory function and downregulating immune system responses to cardiopulmonary surgery and extracorporeal circulation. Patients undergoing cardiac surgery were administered pre-surgery acetylcysteine (loading dose, 72 milligrams/kilogram (mg/kg) intravenously over 1 hour; continuous infusion of 72 mg/kg over 12 hours (volume 500 milliliters (mL)). After surgery the oxygenation index (partial pressure of oxygen in arterial blood/fractional inspired oxygen (PaO2/FIO2)) was more favorable in patients who had been pre-treated with NAC. The increase in plasma neutrophil elastase activity was moderated in the NAC group compared with controls. Interleukin-8 and myeloperoxidase concentrations were lower, and glutathione (GSH) levels more stable in NAC-treated patients (De Backer et al, 1996).

30

Otitis media 中耳炎

1) Overview

FDA Approval: Adult, no; Pediatric, no

Efficacy: Pediatric, Evidence is inconclusive

Recommendation: Pediatric, Class IIb

Strength of Evidence: Pediatric, Category B

2) Summary:

Acetylcysteine reduced the need for reinsertion of ventilation tubes in children with recurrent otitis media with effusion (Ovesen et al, 2000).

3) Pediatric:

a) Instillation of N-acetylcysteine (NAC) into the ears of children undergoing insertion of ventilation tubes (VT) for otitis media with effusion (OME) tended to lengthen the time until VT extrusion and significantly reduced the rate of recurrence of OME requiring reinsertion of VTs. In a randomized, double-blind, placebo-controlled trial, 75 children aged 1 to 7 years undergoing bilateral VT insertion for OME were randomized to receive either NAC (Mucomyst solution 20 milligrams/milliliter) or placebo (vehicle only) in one ear (instilled through a tube) at the time of tube insertion. The contralateral ear was treated only with VT insertion. NAC or placebo treatments were repeated on the third and seventh postoperative days. Time to VT extrusion tended to be longer in the NAC-treated ears than in placebo- treated ears (9 vs 7 months) but the difference was not significant. Recurrence of OME was also not less in NAC- treated than in placebo-treated ears. However, persistent OME requiring re-insertion of VTs was significantly less frequent in NAC-treated ears than in placebo-treated ears (14% vs 37%, p less than 0.025) and also in untreated ears of the NAC group than in untreated ears of the placebo group (19% vs 45%). The total number of episodes of middle ear problems was significantly lower in the NAC group than in the placebo group (p less than 0.025), resulting in significantly fewer clinic visits by children in the NAC group (p=0.0383) during follow- up (11 to 39 months) (Ovesen et al, 2000).

31

Radiographic contrast agent nephropathy; Prophylaxis 預防顯影劑造成腎毒性

1) Overview

FDA Approval: Adult, no; Pediatric, no

Efficacy: Adult, Evidence is inconclusive

Recommendation: Adult, Class IIb

Strength of Evidence: Adult, Category A

2) Summary:

Reduced the incidence of contrast-induced nephropathy in patients with normal baseline renal function undergoing primary angioplasty secondary to acute myocardial infarction in a randomized, placebo-controlled clinical trial (Marenzi et al, 2006)
A meta-analysis of 13 randomized, placebo-controlled clinical trials did not find convincing evidence that N-acetylcysteine protects against contrast-induced nephropathy in patients with baseline renal insufficiency (Zagler et al, 2006).
Acetylcysteine prevented radiographic contrast agent-induced reductions of renal function in renally impaired patients undergoing computed tomographic imaging with a nonionic, low-osmolality radiographic contrast agent (Tepel et al, 2000).
In addition, a randomized, 2-center, double-blind study of 326 patients with chronic kidney disease, volume supplementation by sodium bicarbonate plus N-acetylcysteine (NAC) was superior to the combination of normal saline with NAC alone or with the addition of ascorbic acid in preventing contrast agent-induced nephrotoxicity (CIN) in patients at medium to high risk (Briguori et al, 2007).

3) Adult:

a) In Patients with Normal Baseline Renal Function

1) N-acetylcysteine reduced the incidence of contrast-induced nephropathy in patients undergoing primary angioplasty secondary to acute myocardial infarction in a randomized, placebo-controlled clinical trial. Patients (n=354; mean age, 62 +/- 12 years) who presented within 12 hours (or within 18 hours in patients with cardiogenic shock) of ST-segment elevation acute myocardial infarction were randomized to receive standard-dose N-acetylcysteine (600 milligrams (mg) intravenously (IV) before angioplasty followed by 600 mg orally twice daily for 48 hours after angioplasty; total dose, 3000 mg), high-dose N-acetylcysteine (1200 mg IV before angioplasty followed by 1200 mg orally twice daily for 48 hours after angioplasty; total dose, 6000 mg), or placebo. All patients received hydration following angioplasty, consisting of normal saline 1 milliliter/kilogram/hour (mL/kg/h) (or 0.5 mL/kg/h in patients with overt heart failure) for 12 hours. The primary endpoint was contrast-induced nephropathy, defined as an increase in serum creatinine (SCr) of 25% or more over baseline within 72 hours after angioplasty. Contrast-induced nephropathy occurred in 33% of patients (n=119) who received placebo, 15% of patients (n=115) who received standard-dose N-acetylcysteine, and 8% of patients (n=118) who received high-dose N-acetylcysteine (p < 0.001). When using an absolute rise in SCr of at least 0.5 mg/deciliter (dL) as the definition of contrast-induced nephropathy, the incidences were 18%, 6%, and 3% in the placebo, standard-dose, and high-dose groups, respectively (p < 0.001). After multivariate analysis, the odds ratio (OR) of contrast-induced nephropathy for the control group compared to the standard-dose group was 2.6 (95% confidence interval (CI), 1.3-5.18; p=0.007) and the OR for the control group compared to the high-dose group was 5.78 (95% CI, 2.56-13.16; p < 0.001). In-hospital mortality was significantly reduced for the high-dose group compared to the placebo group (OR, 5.43; 95% CI, 1.24-23.81; p=0.03) but not for the standard-dose group compared to the placebo group (OR, 1.85; 95% CI, 0.54-6.37; p=0.32). For a combined endpoint of death, acute renal failure requiring temporary renal replacement therapy, or the need for mechanical ventilation during the acute phase of myocardial infarction, the rates were 18%, 7%, and 5% in the placebo, standard-dose, and high-dose groups, respectively (p=0.002). A transient systemic rash was noted in one patient in the standard-dose group (Marenzi et al, 2006).

b) In Patients with Baseline Renal Insufficiency

1) In a randomized, 2-center, double-blind study (Renal Insufficiency Following Contrast Media Administration trial (REMEDIAL)) in patients with chronic kidney disease, volume supplementation by sodium bicarbonate plus N-acetylcysteine (NAC) was superior to the combination of normal saline with NAC alone or with the addition of ascorbic acid in preventing contrast agent-induced nephrotoxicity (CIN) in patients at medium to high risk. Patients (n=326) with serum creatinine of 2 or greater milligrams per deciliter (mg/dL) and/or estimated glomerular filtration rate of less than 40 milliliters per minute per 1.73 squared meter (mL/min/1.73 m(2)), were randomly assigned to prophylactic administration of 0.9% saline infusion plus NAC (n=111), sodium bicarbonate infusion plus NAC (n=108), and 0.9% saline plus ascorbic acid plus NAC (n=107). The primary end point was the development of CIN, defined as an increase of 25% or greater in the creatinine concentration 48 hours after the procedure or the need for dialysis . A nonionic, iso-osmolar contrast agent (iodixanol) was used in all patients. Overall, the saline plus NAC, the bicarbonate plus NAC and the saline plus NAC plus ascorbic acid groups had similar amount of contrast media administered (179 +/- 102 mL, 169 +/- 92 mL, and 169 +/- 94 mL (mean +/- SD), respectively; p=0.69) and had similar mean contrast nephropathy risk scores (9.1 +/- 3.4, 9.5 +/- 3.6, and 9.3 +/- 3.6; p=0.21). CIN developed in 9.9% (11/111) of patients in the saline plus NAC group, in 1.9% (2/108) of patients in the bicarbonate plus NAC group (p=0.019 by Fisher exact test versus saline plus NAC group), and in 10.3% (11/107) of patients in the saline plus ascorbic acid plus NAC group (p=1 versus saline plus NAC group). An increase of 0.5 mg/dL or greater in the serum creatinine concentration and a decrease of estimated glomerular filtration rate of 25% or greater at 48 hours after contrast exposure (the additional efficacy end points) were observed less often in the bicarbonate plus NAC group than in the saline plus NAC group and saline plus ascorbic acid plus NAC group (Briguori et al, 2007). 
2) A meta-analysis of 13 clinical trials did not find convincing evidence that N-acetylcysteine protects against contrast-induced nephropathy in patients with baseline renal insufficiency. Randomized, placebo-controlled trials were included if patients had a serum creatinine (SCr) level of more than 1.2 milligrams/deciliter (mg/dL) at baseline, were undergoing coronary angiography, and were receiving intravenous fluids and low-osmolarity nonionic contrast media. The primary endpoint was contrast-induced nephropathy, defined as an increase in SCr of at least 0.5 mg/dL or 25% from baseline to 48 hours. Thirteen trials that consisted of 7 published articles and 6 abstracts included 1892 patients with a mean age ranging from 64 to 73 years and a mean SCr of 1.2 to 2.8 mg/dL. Oral doses of N-acetylcysteine ranged from 400 mg twice daily for 4 doses to 1500 mg twice daily for 4 doses and intravenous doses included a one-time dose of 500 mg prior to the procedure to 150 mg/kilograms (kg) prior to the procedure followed by 50 mg/kg over 4 hours. Significant heterogeneity (p=0.008) was found among the trial results. The combined relative risk (0.68; 95% confidence interval (CI), 0.46-1.01) for developing contrast-induced nephropathy was not statistically significant. Four of the 13 trials found statistically significant reductions in contrast-induced nephropathy in patients who received N-acetylcysteine. After adding a trial to the analysis that included patients undergoing CT scan, a statistically significant benefit was found (RR, 0.64; 95% CI, 0.42-0.96). Exclusion of trials that used intravenous N-acetylcysteine did not alter the results (Zagler et al, 2006).
3) N-acetylcysteine did not improve rates of contrast-induced nephropathy in patients with chronic renal impairment undergoing angiography in a randomized, double-blind, placebo-controlled clinical trial. Patients (n=61) with baseline serum creatinine (SCr) greater than 1.5 milligrams/deciliter (mg/dL) or creatinine clearance below 50 milliliters/minute (mL/min; Cockroft-Gault formula) who were undergoing same-day coronary or peripheral angiographic diagnostic or interventional procedure were randomized to receive N-acetylcysteine 1200 milligrams (mg) diluted in 125 mL of orange juice orally 3 hours before and 3 hours after catheterization (n=33) or placebo (n=28). All patients received hydration with normal saline 4 milliliters/kilogram/hour (mL/kg/h) for 3 hours before the procedure and 2 mL/kg/h for 6 hours after. The primary endpoint was contrast-induced nephropathy, defined as a SCr increase of more than 0.5 mg/dL 48 hours after the procedure. No significant differences were found in the rate of contrast-induced nephropathy in the N-acetylcysteine group (3%) compared to the placebo group (7.1%; relative risk , 0.42; 95% confidence interval, 0.06-3.1; p=0.59). At 48 hours, a significant difference in the change in SCr was observed between groups (N-acetylcysteine group, -0.07 mg/dL; placebo group, +0.09 mg/dL; p=0.04). No significant differences were found in the length of hospitalization, a combined event rate (readmission for acute renal failure or dialysis requirement or death within 30 days), or adverse events (Balderramo et al, 2004).
4) Prophylactic use of acetylcysteine (ACC) significantly reduced the risk of radiographic contrast agent-induced reductions in renal function, in patients with baseline renal insufficiency. In a randomized, double-blind, clinical study, patients with baseline renal insufficiency (mean serum creatinine concentrations equal to 2.4 milligrams/deciliter (mg/dL)) prior to undergoing computer tomography with a radiographic contrast agent (RCA) were assigned to receive 2 daily oral doses of either placebo (n=42) or ACC 600 mg (n=41), given on the day before and the day of contrast agent administration. All patients received concomitant intravenous hydration with 1 mL/kilogram 0.45% saline, for 12 hours prior to, and 12 hours after the administration of contrast agent (75 mL of nonionic, low-osmolality iopromide 0.623 grams/mL). An acute contrast agent-induced reduction in renal function (CAIRF) was defined as an increase in serum creatinine concentration of 0.5 mg/dL 48 hours after RCA administration. Mean serum creatinine concentration increased after 48 hours, from 2.4 to 2.6 mg/dL in patients receiving placebo, compared with a reduction from 2.5 to 2.1 mg/dL in the ACC group; the absolute change in serum creatinine concentration was significantly greater in the placebo group (p less than 0.001). Patients receiving placebo had increases after 48 hours in mean serum urea nitrogen concentration (BUN; from 44 to 47 mg/dL), whereas BUN significantly declined in the ACC group (from 51 to 44 mg/dL; p less than 0.001). CAIRF occurred in 9 of 42 (21%) patients receiving placebo compared with 1 of 41 patients (2%) receiving ACC (p=0.01, relative risk=0.1; 95% confidence interval, 0.2 to 0.9). In a sub-group of patients with baseline serum creatinine concentrations greater than 2.5 mg/dL, 5 of 12 (42%) placebo-group patients developed CAIRF compared with none of 13 patients receiving ACC (p=0.02). Transient dizziness and gastrointestinal discomfort were the only adverse events reported for both groups (Tepel et al, 2000).

32

Respiratory tract infection 呼吸道感染

1) Overview

FDA Approval: Adult, no; Pediatric, no

Efficacy: Adult, Evidence is inconclusive; Pediatric, Evidence is inconclusive

Recommendation: Adult, Class IIb; Pediatric, Class IIb

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

2) Summary:

Several reports describe the effectiveness of the combination of acetylcysteine and cefuroxime in the treatment of respiratory tract infections in infants (Ramenghi et al, 1984), children (Santagelo et al, 1985)(Ramenghi et al, 1984) and adults (Fogliardi et al, 1984; Dal Negro et al, 1985; Bonavita, 1985).
In elderly and/or debilitated patients (n=262), oral N-acetylcysteine 600 milligrams twice daily throughout the cold and flu season (6-month duration) significantly decreased the incidence of symptomatic influenza cases (De Flora et al, 1997).

3) Adult:

a) Several reports describe the effectiveness of the combination of acetylcysteine and cefuroxime in the treatment of respiratory tract infections in infants (Ramenghi et al, 1984), children (Santagelo et al, 1985)(Ramenghi et al, 1984) and adults (Fogliardi et al, 1984; Dal Negro et al, 1985; Bonavita, 1985).
b) Acetylcysteine was efficacious in combination with cefuroxime in curing respiratory tract infections. Sixty-five adult patients, 25 with acute bronchopulmonary respiratory tract diseases and 40 with acute exacerbations of chronic respiratory tract infections, were treated by means of intramuscular injection of a combination of 1 g cefuroxime and 300 mg acetylcysteine. Patients were divided into 2 groups according to the acute or chronic nature of their respiratory tract diseases. Positive clinical results were obtained in 62 of the 65 patients. Of a total of 52 pathogens isolated in pretreatment bacteriological tests on sputum cultures, only 3 were still detectable after treatment. Tolerance of the treatment was good in all patients; no side effects of any kind were observed (Dal Negro et al, 1985).
c) In elderly and/or debilitated patients (n=262), oral N-acetylcysteine 600 milligrams twice daily throughout the cold and flu season (6-month duration) significantly decreased the incidence of symptomatic influenza cases. None of the subjects had respiratory disease at baseline or received the influenza vaccine. In the active and control groups, influenza occurred in 29% and 51% of subjects, respectively. Although the rate of seroconversion was similar, only 25% of patients experienced clinical symptoms while on acetylcysteine, as compared to 79% of those on placebo. N-acetylcysteine also enhanced cell-mediated immunity with regard to antigenic skin testing. It is unclear what benefit, if any, acetylcysteine might offer to patients who are appropriately immunized against influenza (De Flora et al, 1997).
d) Acetylcysteine may be beneficial as an adjunct to anti-inflammatory therapy in patients with fibrosing alveolitis (FA). In an open-label case series study, 18 patients with FA were administered acetylcysteine 600 milligrams three times daily for 12 weeks (Behr et al, 1997). Lung function parameters were significantly improved by acetylcysteine in patients on immunosuppressive therapy (p less than 0.01). Bronchoalveolar lavage analysis showed increases in glutathione and decreases in methionine sulfoxide, indicating an antioxidant effect at the alveolar surface. The drug was well tolerated. It was recommended that a placebo-controlled trial be conducted of acetylcysteine as adjunctive therapy in fibrosing alveolitis.

4) Pediatric:

a) One study reported the efficacy of combined cefuroxime (60 to 100 milligrams/kilogram/day) and N-acetylcysteine (20 to 30 milligrams/kilogram/day) for 5 to 10 days in the treatment of lower respiratory tract infection in children. Both drugs were given intramuscularly (IM). Evidence of objective recovery or improvement occurred in 100 of 103 children, with no toxicity being observed. It is speculated that mucolytic therapy with acetylcysteine reduces tracheobronchial secretions which could accumulate in the peripheral bronchi, resulting in mucus plugs which facilitate implantation of bacterial organisms (Santangelo et al, 1985). However, it is unclear if this regimen is superior to cefuroxime alone.
b) In an uncontrolled study, 20 infants ranging in age from 10 months to 2 years suffering from recurrent catarrhal bronchial disease of bacterial origin were successfully treated with a combination of acetylcysteine and cefuroxime, administered intramuscularly at doses of 15 and 50 milligrams/kilogram/day, respectively, for a mean period of 10.4 +/- 3.2 days. Clinical controls showed that the combination produced a prompt, marked reduction in bronchial hypersecretion. The clinical effects, which are described in detail, and the excellent local and systemic tolerability of the combination show it to be a valid form of treatment for bacterial bronchial disease in early infancy (Ramenghi et al, 1984).

33

Sjögren's syndrome 修格連氏症候群

1) Overview

FDA Approval: Adult, no; Pediatric, no

Efficacy: Adult, Evidence is inconclusive

Recommendation: Adult, Class III

Strength of Evidence: Adult, Category B

2) Summary:

Acetylcysteine appears to lack efficacy in the treatment of Sjogren's syndrome (Nahir, 1989).

3) Adult:

a) One controlled study points to a limited role for acetylcysteine in treating Sjogren's syndrome. A trial was conducted in 10 patients with Sjogren's syndrome treated orally with N-acetylcysteine for 14 days (Nahir, 1989). The control group consisted of eight patients with rheumatoid arthritis but without xerostomia and/or keratoconjuctivitis sicca. Subjective ocular and oral improvement was marginal; no significant change in objective parameters (ophthalmic or oral) was registered except for an increase in enzyme concentration. No serious side effects were reported.
b) Among 20 patients with Sjogren's syndrome whose keratoconjunctivitis did not respond to replacement therapy with artificial tears, 6 patients improved with 12 months of topical treatment with acetylcysteine 5%, 13 showed no change, and one worsened (Williamson et al, 1974).

34

Tracheostomy care 氣切照護

FDA Labeled Indication
1) Overview

FDA Approval: Adult, yes; Pediatric, yes

Efficacy: Adult, Effective; Pediatric, Effective

Recommendation: Adult, Class IIb; Pediatric, Class IIb

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 including for tracheostomy care (Prod Info acetylcysteine inhalation solution, 2004).

35

Unverricht-Lundborg syndrome

1) Overview

FDA Approval: Adult, no; Pediatric, no

Efficacy: Adult, Evidence is inconclusive

Recommendation: Adult, Class IIb

Strength of Evidence: Adult, Category C

2) Summary:

A 40-year-old man with a history of 27 years of tonic-clonic seizures and progressive deterioration of speech and cognition due to genetically confirmed Unverricht-Lundborg disease (an autosomal recessive degenerative disorder), showed dramatic improvement when treated with N-acetylcysteine (NAC) 3 grams/day and antioxidant vitamins (Selwa, 1999).

3) Adult:

a) A 40-year-old man with a history of 27 years of tonic-clonic seizures and progressive deterioration of speech and cognition due to genetically confirmed Unverricht-Lundborg disease (an autosomal recessive degenerative disorder), showed dramatic improvement when treated with N-acetylcysteine (NAC) 3 grams/day and antioxidant vitamins. Prior to treatment with NAC, he manifested severe action myoclonus, worsening with sensory stimulation of any type, and spoke in one- to three-word phrases. He could take only one or two steps, with support by attendants. One week after beginning NAC treatment, he was walking all day in the workshop, his tremors had diminished significantly, and he was talking more. At a meeting, he reportedly talked for 1 hour, fluently. After 4.5 months of sustained improvement, he stopped taking NAC for a week because of the unappealing taste. Within 3 days, his caretakers noticed reduced fluency of speech and deterioration of his ability to walk. He restarted medication and improvement was evident in 2 days. Prior to NAC treatment, he had experienced about 10 generalized seizures per year; during 10 months of taking NAC, he had only 2 atypical, brief (5- to 10-second) spells and no generalized seizures (Selwa, 1999).