Katherine Welter, MD

Background: Naloxone is an opioid antagonist that works to treat opioid overdose. Few randomized trials have assessed the efficacy of intranasal administration, whereas more data have been published supporting use of intramuscular naloxone. This prospective trial examines the ability of the same dose (800 mcg per 1 mL solution) of intranasal naloxone vs. intramuscular naloxone at managing opioid overdose.

Study design: Double-blind double-dummy randomized clinical trial.

Setting: Single supervised injection center in Sydney.

Synopsis: In this study, 197 participants with opioid overdose were randomized to intramuscular or intranasal naloxone. If the patient did not respond to either (GSC score less than 13, RR less than 10, or oxygen saturation less than 95%), a rescue dose of intramuscular naloxone was given. Participants who received the intramuscular naloxone were less likely to need the rescue dose (8.6% vs. 23.1%; odds ratio, 0.35; P = .002). The time to achieve an RR greater than 10 (15 vs. 8 minutes) and GSC score greater than 13 (17 vs. 8 minutes) was longer in the intranasal than the intramuscular group. Limitations include the setting of a controlled environment. Also, this protocol called for an initial 5 minutes of ventilation prior to randomization, which selected for more severe overdose cases in the overall study population. More studies are needed to assess efficacy in the field, needlestick injuries, and larger intranasal doses.

Bottom line: Intranasal naloxone effectively reverses opioid overdose but not as effectively as intramuscular naloxone at the same dose.

Citation: Dietze P et al. Effect of intranasal vs intramuscular naloxone on opioid overdose: A randomized clinical trial. JAMA Netw Open. 2019;2:e1914977. doi: 10.1001/jamanetworkopen.2019.14977.

Dr. Welter is a hospitalist at Northwestern Memorial Hospital and instructor of medicine, Feinberg School of Medicine, both in Chicago.

Background: Naloxone is an opioid antagonist that works to treat opioid overdose. Few randomized trials have assessed the efficacy of intranasal administration, whereas more data have been published supporting use of intramuscular naloxone. This prospective trial examines the ability of the same dose (800 mcg per 1 mL solution) of intranasal naloxone vs. intramuscular naloxone at managing opioid overdose.

Study design: Double-blind double-dummy randomized clinical trial.

Setting: Single supervised injection center in Sydney.

Synopsis: In this study, 197 participants with opioid overdose were randomized to intramuscular or intranasal naloxone. If the patient did not respond to either (GSC score less than 13, RR less than 10, or oxygen saturation less than 95%), a rescue dose of intramuscular naloxone was given. Participants who received the intramuscular naloxone were less likely to need the rescue dose (8.6% vs. 23.1%; odds ratio, 0.35; P = .002). The time to achieve an RR greater than 10 (15 vs. 8 minutes) and GSC score greater than 13 (17 vs. 8 minutes) was longer in the intranasal than the intramuscular group. Limitations include the setting of a controlled environment. Also, this protocol called for an initial 5 minutes of ventilation prior to randomization, which selected for more severe overdose cases in the overall study population. More studies are needed to assess efficacy in the field, needlestick injuries, and larger intranasal doses.

Bottom line: Intranasal naloxone effectively reverses opioid overdose but not as effectively as intramuscular naloxone at the same dose.

Citation: Dietze P et al. Effect of intranasal vs intramuscular naloxone on opioid overdose: A randomized clinical trial. JAMA Netw Open. 2019;2:e1914977. doi: 10.1001/jamanetworkopen.2019.14977.

Dr. Welter is a hospitalist at Northwestern Memorial Hospital and instructor of medicine, Feinberg School of Medicine, both in Chicago.

Background: Naloxone is an opioid antagonist that works to treat opioid overdose. Few randomized trials have assessed the efficacy of intranasal administration, whereas more data have been published supporting use of intramuscular naloxone. This prospective trial examines the ability of the same dose (800 mcg per 1 mL solution) of intranasal naloxone vs. intramuscular naloxone at managing opioid overdose.

Study design: Double-blind double-dummy randomized clinical trial.

Setting: Single supervised injection center in Sydney.

Synopsis: In this study, 197 participants with opioid overdose were randomized to intramuscular or intranasal naloxone. If the patient did not respond to either (GSC score less than 13, RR less than 10, or oxygen saturation less than 95%), a rescue dose of intramuscular naloxone was given. Participants who received the intramuscular naloxone were less likely to need the rescue dose (8.6% vs. 23.1%; odds ratio, 0.35; P = .002). The time to achieve an RR greater than 10 (15 vs. 8 minutes) and GSC score greater than 13 (17 vs. 8 minutes) was longer in the intranasal than the intramuscular group. Limitations include the setting of a controlled environment. Also, this protocol called for an initial 5 minutes of ventilation prior to randomization, which selected for more severe overdose cases in the overall study population. More studies are needed to assess efficacy in the field, needlestick injuries, and larger intranasal doses.

Bottom line: Intranasal naloxone effectively reverses opioid overdose but not as effectively as intramuscular naloxone at the same dose.

Citation: Dietze P et al. Effect of intranasal vs intramuscular naloxone on opioid overdose: A randomized clinical trial. JAMA Netw Open. 2019;2:e1914977. doi: 10.1001/jamanetworkopen.2019.14977.

Dr. Welter is a hospitalist at Northwestern Memorial Hospital and instructor of medicine, Feinberg School of Medicine, both in Chicago.

Background: Hyponatremia caused by SIADH is common in hospitalized patients, and most evidence for treatment comes from noncontrolled studies. This study aims to investigate the efficacy and safety of fluid restriction compared with furosemide, with or without NaCl supplementation, for treating SIADH.

Study design: Open-label randomized controlled trial.

Setting: Single center in Thailand.

Synopsis: There were 92 participants randomized to fluid restriction alone, fluid restriction and furosemide, or fluid restriction, furosemide, and NaCl supplementation. The authors assessed the primary outcome, change in sodium, at 4, 7, 14, and 28 days (baseline mean Na 125 mmol/L). By day 4, all groups had a significant increase in sodium (mean delta 5 mmol/L). The time to achieve a safe sodium level (Na less than 130 mmol/L) was not different among groups. Acute kidney injury was most common in patients who received furosemide and NaCl supplementation, compared with the fluid restriction and fluid restriction plus furosemide groups (32%, 10%, 17%, respectively; P = .07). Hypokalemia was also most common in the furosemide and NaCl group (42%, 13%, 23%, respectively; P = .01). Limitations include open-label study design, poor fluid restriction adherence (63% overall), and inflexible treatment regimens that excluded treatment with oral potassium.

Bottom line: In treatment of hyponatremia caused by SIADH, there was no benefit to adding furosemide with or without NaCl supplementation to fluid restriction. However, there was potential associated risk of acute kidney injury and hypokalemia.Citation: Krisanapan P et al. Efficacy of furosemide, oral sodium chloride, and fluid restriction for treatment of syndrome of inappropriate antidiuresis (SIADH): An open-label randomized controlled study (the EFFUSE-FLUID trial). Am J Kidney Dis. 2020 Aug;76(2):203-12. doi: 10.1053/j.ajkd.2019.11.012.

Dr. Welter is a hospitalist at Northwestern Memorial Hospital and instructor of medicine, Feinberg School of Medicine, both in Chicago.

Background: Hyponatremia caused by SIADH is common in hospitalized patients, and most evidence for treatment comes from noncontrolled studies. This study aims to investigate the efficacy and safety of fluid restriction compared with furosemide, with or without NaCl supplementation, for treating SIADH.

Study design: Open-label randomized controlled trial.

Setting: Single center in Thailand.

Synopsis: There were 92 participants randomized to fluid restriction alone, fluid restriction and furosemide, or fluid restriction, furosemide, and NaCl supplementation. The authors assessed the primary outcome, change in sodium, at 4, 7, 14, and 28 days (baseline mean Na 125 mmol/L). By day 4, all groups had a significant increase in sodium (mean delta 5 mmol/L). The time to achieve a safe sodium level (Na less than 130 mmol/L) was not different among groups. Acute kidney injury was most common in patients who received furosemide and NaCl supplementation, compared with the fluid restriction and fluid restriction plus furosemide groups (32%, 10%, 17%, respectively; P = .07). Hypokalemia was also most common in the furosemide and NaCl group (42%, 13%, 23%, respectively; P = .01). Limitations include open-label study design, poor fluid restriction adherence (63% overall), and inflexible treatment regimens that excluded treatment with oral potassium.

Bottom line: In treatment of hyponatremia caused by SIADH, there was no benefit to adding furosemide with or without NaCl supplementation to fluid restriction. However, there was potential associated risk of acute kidney injury and hypokalemia.Citation: Krisanapan P et al. Efficacy of furosemide, oral sodium chloride, and fluid restriction for treatment of syndrome of inappropriate antidiuresis (SIADH): An open-label randomized controlled study (the EFFUSE-FLUID trial). Am J Kidney Dis. 2020 Aug;76(2):203-12. doi: 10.1053/j.ajkd.2019.11.012.

Dr. Welter is a hospitalist at Northwestern Memorial Hospital and instructor of medicine, Feinberg School of Medicine, both in Chicago.

Background: Hyponatremia caused by SIADH is common in hospitalized patients, and most evidence for treatment comes from noncontrolled studies. This study aims to investigate the efficacy and safety of fluid restriction compared with furosemide, with or without NaCl supplementation, for treating SIADH.

Study design: Open-label randomized controlled trial.

Setting: Single center in Thailand.

Synopsis: There were 92 participants randomized to fluid restriction alone, fluid restriction and furosemide, or fluid restriction, furosemide, and NaCl supplementation. The authors assessed the primary outcome, change in sodium, at 4, 7, 14, and 28 days (baseline mean Na 125 mmol/L). By day 4, all groups had a significant increase in sodium (mean delta 5 mmol/L). The time to achieve a safe sodium level (Na less than 130 mmol/L) was not different among groups. Acute kidney injury was most common in patients who received furosemide and NaCl supplementation, compared with the fluid restriction and fluid restriction plus furosemide groups (32%, 10%, 17%, respectively; P = .07). Hypokalemia was also most common in the furosemide and NaCl group (42%, 13%, 23%, respectively; P = .01). Limitations include open-label study design, poor fluid restriction adherence (63% overall), and inflexible treatment regimens that excluded treatment with oral potassium.

Bottom line: In treatment of hyponatremia caused by SIADH, there was no benefit to adding furosemide with or without NaCl supplementation to fluid restriction. However, there was potential associated risk of acute kidney injury and hypokalemia.Citation: Krisanapan P et al. Efficacy of furosemide, oral sodium chloride, and fluid restriction for treatment of syndrome of inappropriate antidiuresis (SIADH): An open-label randomized controlled study (the EFFUSE-FLUID trial). Am J Kidney Dis. 2020 Aug;76(2):203-12. doi: 10.1053/j.ajkd.2019.11.012.

Dr. Welter is a hospitalist at Northwestern Memorial Hospital and instructor of medicine, Feinberg School of Medicine, both in Chicago.