Purpose: Conflicting results exist regarding the efficacy of N-acetyl cysteine (NAC) in sepsis treatment. A pivotal factor affecting the therapeutic potency of NAC in sepsis is timing and dosing of its infusion. We aimed to assess the effect of NAC on redox status of patients with sepsis and to compare its efficacy in intermittent and continuous infusion with the objective of developing the infusion regimen and optimizing the timing. Materials and Methods: A prospective, randomized clinical trial was designed to compare the antioxidative effect of NAC in intermittent infusion group (IV: 25 mg/kg bolus and then 25 mg/kg/8 hours 3 times) and continuous infusion group (IV: 25 mg/kg bolus and then 75 mg/kg over 24 hours) in 60 critically ill patients with sepsis (20 patients in each group). Blood samples were collected immediately before and after intervention for total antioxidant capacity (TAC) and malondialdehyde (MDA) assessment. Results: N-acetyl cysteine considerably increased TAC levels in both intermittent (0.68 ± 0.60; P value = .036) and continuous (0.69 ± 0.64; P value = .015) infusion groups when compared to placebo (0.61 ± 0.10); however, the difference in TAC levels between the intermittent and the continuous infusion did not reach statistical significance ( P value = .942). Likewise, NAC treatment decreased MDA levels in both intermittent (19.45 ± 4.18; P value = 0.001) and continuous (22.47 ± 6.68; P value = .002) infusion groups when compared to placebo (31.76 ± 11.06), while the difference in MDA levels between the intermittent and the continuous infusion did not reach statistical significance ( P value = .481). Conclusion: Our data confirmed the antioxidative effect of NAC treatment in patients with sepsis, with no significant difference in intermittent and continuous infusion.
preparations of vasopressor therapies, 2 push-dose preparations and a peripheral continuous infusion. PDPs were prepared according to 2 techniques. The first is a "dirty" preparation utilizing a saline flush and cardiac epinephrine syringes, physically mixing the 2-in-1 syringe. The second method of preparation is a best practice according to the Institute for Safe Medication Practices (ISMP) and utilized bacteriostatic normal saline and cardiac epinephrine syringes for admixture. Norepinephrine infusions were compounded to have a final concentration of 4mg/ 250mL. Physicians (including both ED residents and attendings) were not asked to prepare an IV infusion, due to their limited familiarity with IV pumps. The timer was initiated on a count down and was stopped when the vasopressor therapy had been successfully administered through an IV line in a mannequin arm. After the completion of all 3 preparations, a survey was completed recording participants' professions, preferred method of preparation and years of job experience. Results: Overall 20 participants were included, 10 physicians, 6 registered nurses and 4 pharmacists. On average, a peripheral IV infusion took almost twice as long as either PDP preparation. Median preparation times for all professions were 58, 66 and 119 seconds (dirty, clean and IV respectively). Clean PDP took an average of 5 seconds longer to prepare when compared to dirty with dirty PDP being the preferred method of preparation by 55% of participants. Conclusions: The use of PDP can be considered in patients as a bridge to continuous infusion; however, it may be just as beneficial to start continuous infusion to prevent further decompensation, given the compounding time differences between PDP and continuous preparations. Although admixture instructions were provided, there remained variations in the preparation techniques of both PDP preparations. The potential for medication errors remains high, with variations in preparation techniques. This study has demonstrated further evidence for the need of institutional standardization of PDP preparations.
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