Characteristics and outcomes of intensive care patients receiving metaraminol infusion—a retrospective observational cohort study

Abstract

There is limited published data on metaraminol dosing, duration of therapy and clinical outcomes for critically ill patients. We conducted a retrospective cohort study across two tertiary intensive care units (ICUs) and included all patients who received a metaraminol infusion between 26 August 2016 and 31 December 2021. The primary outcome of this study was to describe the characteristics and outcomes of patients who receive metaraminol in ICU. Secondary outcomes included a range of pharmacological and physiological measures. We studied 1261 patients, which represented 6.7% of ICU admissions during the study period. Most (85.4%) patients were unplanned admissions and less than 40% required mechanical ventilation. ICU and hospital mortality were low (7.4% and 12.4% respectively). Median total infusion duration for metaraminol was 10 (interquartile range, 3–24) h. Median dose range was 1 mg/h (16 µg/min) to 6 mg/h (100 µg/min). Almost three-fifths of these patients subsequently transitioned to norepinephrine (noradrenaline), which commenced at a median time of 7 h after initiation of metaraminol. Hourly heart rate, mean arterial pressure and respiratory rate remained very stable during infusion of metaraminol and median urine output remained greater than 30 ml/h for the first 24 h. In conclusion, patients who received metaraminol by infusion in the ICU had a low severity of illness and risk of mortality. Dosing of metaraminol was conservative and clinicians frequently transitioned to norepinephrine early despite the low doses infused. Metaraminol effectively maintained blood pressure with no associated tachycardia or significant drop in urine output and no clinical evidence of tachyphylaxis.

Keywords

Hypotension intensive care metaraminol vasopressor vasodilatory shock

Introduction

Metaraminol is a commonly used vasopressor agent for the management of fluid-refractory hypotension in anaesthesia and intensive care practice in some jurisdictions around the world.^1–3 Although norepinephrine (noradrenaline) is the universally recommended first-line vasopressor for this indication,⁴ clinicians continue to utilise metaraminol as a viable alternative agent, particularly via peripheral infusion.⁵

Metaraminol is a direct alpha-1 agonist and, in low doses, stimulates beta-1 receptors. It also indirectly releases endogenous norepinephrine, acting as a false neurotransmitter to displace norepinephrine from storage vesicles in adrenergic synapses, increasing synaptic and systemic norepinephrine concentration.⁶ Small studies have shown that metaraminol increases systemic and pulmonary vascular resistance⁷ without changes in cardiac index and central venous pressure.⁸

Despite widespread use of metaraminol, there is limited published data on patient selection, dosing, duration of therapy and clinical outcomes to guide its initiation and titration for critically ill patients.⁹ Current practice suggests that clinicians utilise an arbitrary dose or timing threshold for conversion to central access and ongoing alternative vasopressor infusions.^2,10 This is likely due to a dearth of information to guide clinicians on the safe dosing range, adverse events and need for alternative or adjunctive vasopressors.

Accordingly, we conducted a large, two-centre retrospective cohort study of critically ill patients who received a metaraminol infusion for vasodilatory shock in the intensive care unit (ICU). We aimed to describe the characteristics of patients who received metaraminol in the ICU and their clinical outcomes. Our secondary objectives were to describe the haemodynamic and physiological effects of metaraminol, infusion characteristics, including dosing and duration of therapy, and to determine the proportion of patients who were converted to norepinephrine for ongoing vasopressor support.

Methods

Study design and setting

We conducted a retrospective cohort study across two tertiary ICUs in Melbourne, Australia. We included all adult (age ⩾ 18 years) patients admitted to ICU who received a metaraminol infusion between 26 August 2016 and 31 December 2021. No exclusion criteria were applied.

Data collection

Data was sourced from patient medical records and electronic databases and included patient demographics, hospital and ICU admission and discharge details, intensive care treatments, baseline physiological and biochemical parameters, and vasopressor and non-vasopressor infusion data. We collected detailed hourly haemodynamic, biochemical and infusion data from a subgroup of patients where this data was available via their electronic health record.

Outcomes

The primary outcome of this study was to describe patient characteristics and clinical outcomes, including ICU and hospital length of stay and mortality. Secondary outcomes included determining the proportion of patients who were converted to norepinephrine infusion as well as a range of pharmacological outcomes (duration of metaraminol therapy, minimum and maximum metaraminol dose) and physiological outcomes (changes in mean arterial pressure, heart rate, urine output and lactate).

Statistical analysis

Continuous variables are reported as median (interquartile range (IQR)) or mean (standard deviation) and categorical variables as number and percentage. For mean arterial pressure and infusion doses, simple imputation using the last observation carried forward method was used. All analyses were performed in R v.4.0.2 and P <0.05 was considered statistically significant. No assumptions were made regarding the values of any missing data and analyses were conducted on available data only. To identify factors associated with metaraminol use as the sole vasoactive agent at ICU admission, we performed a multivariable logistic regression analysis. We first applied least absolute shrinkage and selection operator (LASSO) regression for variable selection to prevent model overfitting. Variables retained by the LASSO model were then entered into a standard logistic regression to obtain adjusted odds ratios with 95% confidence intervals and P values. Continuous variables were modelled linearly.

Ethics approval

Local institutional ethics approval was provided (Austin Health Human Research Ethics Committee; Project Reference No: HREC/85954/Austin-2022). Requirement for individual informed consent was waived owing to the study’s retrospective nature and use of de-identified data.

Results

Patient characteristics and clinical outcomes

Over the five-year period, 1261 patients were included in the study from 18,819 admissions (6.7% of ICU admissions). Their median age was 65 (IQR 53–76) years (Table 1). The majority of patients were unplanned admissions with roughly one-third admitted to the ICU from the operating room, emergency department and general wards, respectively. Less than one-quarter of the cohort had a diagnosis of sepsis. Chronic kidney disease was the commonest comorbidity, affecting one in seven patients.

Table 1.

Characteristics of the patients at baseline and organ support during intensive care unit stay.

Characteristics	Overall (N = 1261)
Age, years	65.7 (53.5–76.8)
Male sex, n (%)	707/1210 (58.4%)
Body mass index, kg/m²	25.3 (21.1–29.7)
APACHE III score	59.0 (44.0–75.0)
Clinical frailty score	3.0 (3.0–4.0)
Unplanned admission, n (%)	1027/1202 (85.4%)
ICU source of admission, n (%)
Emergency department	367/1261 (29.1%)
Operating room	423/1261 (33.5%)
Ward	339/1261 (26.9%)
Other	132/1261 (10.5%)
Surgical admission, n (%)	406/1201 (33.8%)
Sepsis, n (%)	276/1203 (22.9%)
Admission category, n (%)
Cardiovascular	108/1168 (9.2%)
Cardiovascular surgery	56/1168 (4.8%)
Gastrointestinal	42/1168 (3.6%)
Gastrointestinal surgery	69/1168 (5.9%)
Gynaecological surgery	2/1168 (0.2%)
Haematological	14/1168 (1.2%)
Metabolic	54/1168 (4.6%)
Metabolic surgery	6/1168 (0.5%)
Musculoskeletal surgery	41/1168 (3.5%)
Neurological	57/1168 (4.9%)
Neurological surgery	78/1168 (6.7%)
Renal/genitourinary	35/1168 (3.0%)
Renal/genitourinary surgery	62/1168 (5.3%)
Respiratory	119/1168 (10.2%)
Respiratory surgery	55/1168 (4.7%)
Sepsis	259/1168 (22.2%)
Trauma	63/1168 (5.4%)
Trauma surgery	48/1168 (4.1%)
Coexisting disorders, n (%)
Chronic kidney disease	173/1196 (14.5%)
Chronic respiratory disease	139/1196 (11.6%)
Immunosuppression	137/1196 (11.5%)
Chronic cardiovascular disease	70/1196 (5.9%)
Cirrhosis	69/1196 (5.8%)
Metastatic cancer	68/1196 (5.7%)
Leukaemia	38/1196 (3.2%)
Lymphoma	21/1196 (1.8%)
Hepatic failure	12/1196 (1.0%)
AIDS	3/1196 (0.3%)
Organ support during ICU stay, n (%)
Invasive mechanical ventilation	398/1002 (39.7%)
Renal replacement therapy	77/1010 (7.6%)
Extracorporeal membrane oxygenation	2/1002 (0.2%)
Worst vital signs in the first 24 h of ICU admission
Temperature, °C	37.0 (36.5–37.5)
Heart rate, beats/min	92.0 (80.0–110.0)
Mean arterial pressure, mmHg	60.0 (55.0–67.0)
Urine output, ml	1500.0 (1040.0–2205.0)
Laboratory tests in the first 24 h of ICU admission
pH	7.39 (7.33–7.44)
Lactate, mmol/l	1.9 (1.3–2.9)
Urea, mmol/l	7.8 (5.1–13.1)
Creatinine, µmol/l	94.5 (68.0–161.0)

Data is shown as median (interquartile range) or number (percentage).

AIDS: acquired immunodeficiency syndrome; APACHE: Acute Physiology and Chronic Health Evaluation; ICU: intensive care unit

Overall, less than 40% of patients required mechanical ventilation and less than 8% required renal replacement therapy. Baseline median serum lactate and pH were within normal range for the cohort. Baseline mean arterial pressure was 60 (IQR 55–67) mmHg. Almost 60% of the cohort were discharged home with a median length of ICU stay of 2.7 (IQR 1.7–4.8) days (Table 2). ICU and hospital mortality were low (7.4% and 12.4% respectively).

Table 2.

Clinical outcomes of the patients.

Clinical outcomes	Overall (N = 1261)
Discharged home^a, n (%)	702/1203 (58.4%)
ICU length of stay, days	2.7 (1.7–4.8)
Hospital length of stay, days	11.8 (6.2–21.4)
ICU mortality, n (%)	89/1202 (7.4%)
Hospital mortality, n (%)	149/1203 (12.4%)

Data is shown as median (interquartile range) or number (percentage).

Final disposition of patients not discharged home or deceased, includes transferred to another hospital, rehabilitation facility, chronic care institution, or hospice.

ICU: intensive care unit

Metaraminol infusion characteristics and adjunctive therapies

Metaraminol infusion was commenced early in the ICU at a median time of 2 (IQR 0–9) h (Table 3). Total infusion duration was short, with a median time of 10 (IQR 3–24) h. Median dose range was 1 mg/h (16 µg/min) to 6 mg/h (100 µg/min). The maximum dose infused was 12 mg/h (200 µg/min). The mean dose was 3.5 mg/h (58 µg/min) (Figure 1).

Table 3.

Characteristics of metaraminol infusion.

Characteristics	Overall (N = 1261)
Number of metaraminol infusions per patient^a	1.0 (1.0–1.0)
Patients with ⩾2 episodes of metaraminol infusion	24/1261 (1.9%)
Hours between ICU admission and start of metaraminol	2.0 (0.0–9.0)
Hours between ICU admission and cessation of metaraminol	16.0 (6.0–35.0)
Total duration of metaraminol infusion, h	10.0 (3.0–24.0)
Dose of metaraminol per patient
Mean dose, mg/h	3.5 (2.0–5.9)
Highest dose, mg/h	6.0 (4.0–10.0)
Lowest dose, mg/h	1.0 (0.0–3.0)
Total dose, mg	24.0 (11.0–50.7)

Data is shown as median (interquartile range) or number (percentage).

Total number of metaraminol infusions administered during the same ICU admission.

ICU: intensive care unit

Figure 1.

Dose of metaraminol administration.

Metaraminol was used as the first-line vasopressor in over 90% of patients in this cohort (Supplemental material Table 1 online). Almost three-fifths of these patients subsequently required an alternative vasopressor, which was almost universally norepinephrine and was commenced at a median time of 7 h after commencement of metaraminol. Once commenced, the median duration of norepinephrine infusion was 54 h but remained at relatively low doses (mean dose 5 µg/min). Around one in 10 patients required vasopressin as an adjunctive vasopressor, or an inotropic agent (i.e. epinephrine (adrenaline) or milrinone) (Supplemental Table 2). Frail patients and unplanned admissions to the ICU were less likely to convert to an alternative vasopressor. Septic patients and those requiring more intensive therapies such as invasive mechanical ventilation and renal replacement therapy were more likely to convert (Supplemental Table 4).

Haemodynamic and physiological effects

Detailed haemodynamic data was drawn from a subgroup of 182 patients. Hourly heart rate, systolic, diastolic and mean blood pressure and respiratory rate remained very stable during infusion of metaraminol (Figure 2). Median heart rate was between 74 and 77 beats/min and mean arterial pressure was between 71 and 76 mmHg. Median serial lactate measurements remained less than 2 mmol/l and urine output remained greater than 30 ml/h for the first 24 h (Figure 3 and Supplemental Table 3).

Figure 2.

Trends in blood pressure, heart rate and respiratory rate during the first 24 h of metaraminol infusion.

Figure 3.

Urine output over time after start of metaraminol infusion.

Discussion

Key findings

In this study, we found that patients who received metaraminol infusion were most commonly unplanned admissions to the ICU, with few comorbidities and a low severity of illness. Metaraminol was commenced early in their ICU admission, as a first-line vasopressor, but for a short duration only. Metaraminol effectively maintained mean arterial pressure with no associated tachycardia or significant change in urine output in this low acuity cohort. The prescribed dose range of metaraminol was narrow and the majority of patients transitioned to norepinephrine within 8 h. ICU length of stay was relatively short and mortality was low in this cohort of patients. Overall, utilisation of metaraminol was low with fewer than one in 15 ICU patients receiving this vasopressor therapy.

Relationship with previous studies

Our study expands and validates the findings of similar epidemiological studies of metaraminol use in the ICU. In a single-centre retrospective study of 152 patients, Sardaneh et al¹¹ describe a patient population with similar median Acute Physiology and Chronic Health Evaluation (APACHE) III scores and admission source. Notably, in their study, median duration of metaraminol infusion prior to conversion to norepinephrine was similar at 5 (IQR 2–10) h and the proportion of patients who converted to norepinephrine was also comparable (47% vs 56%). Median maximum dose was lower than the median dose range in our cohort at 4 mg/h.

In contrast, a much larger, recently published observational study by Zimsen et al¹² of 1963 patients from 12 ICUs in Queensland, Australia demonstrates subtle, yet important, differences in metaraminol prescription. In this cohort, patients had lower median APACHE III scores (51 vs 59) and a greater likelihood of admission from the operating theatre (52%) but received metaraminol at higher doses (median maximum dose 10 mg/h, IQR 4–30) and were less likely to convert to norepinephrine (35%). Interestingly, even in this cohort, patients who did convert to norepinephrine did so at a median time of 6 h. ICU mortality was also low in this cohort (5.9%).

These two studies, along with our findings, confirm that metaraminol is preferentially prescribed to patients with lower acuity critical illness. There is, however, some variation in metaraminol prescription practices in Australia. Utilisation of metaraminol appears to vary depending on ICU type. Tertiary ICUs such as those described in our study and the Sardaneh et al study suggest lower utilisation in such centres (around 6% of all ICU admissions in both studies). The Zimsen et al study supports this finding and reports greater utilisation in regional centres compared with tertiary units (odds ratio 1.47). This might reflect barriers to central line insertion in smaller centres and therefore greater utilisation of peripheral metaraminol for vasopressor support.¹²

Whilst the decision to convert to norepinephrine seems to consistently occur within 8 h of infusion, there appears to be a lower need to convert if higher doses of metaraminol are considered. Current guidelines recommend a maximum metaraminol dose of 10 mg/h,^13,14 although there are no studies to support this upper infusion dose limit. In the Zimsen et al study, metaraminol doses of up to 30 mg/h were administered prior to conversion to norepinephrine. Another retrospective cohort study,¹⁵ of critically ill patients with neurological diagnoses requiring peripheral vasopressor support, found that when metaraminol was prescribed at doses up to 20 mg/h, only 12.8% of patients subsequently required central venous access and an alternative vasopressor.

A further important consideration in determining a threshold for conversion to norepinephrine is dose equivalency. Whilst recent studies suggest a metaraminol:norepinephrine dose equivalency of 12.5:1,¹⁶ there is significant variance,^7,16 and this predisposes as many as one-third of patients¹⁷ to hypotension during vasopressor conversion. Given this adverse finding, metaraminol monotherapy might be a safer option for low-risk patients such as those described in this cohort. Finally, the cost implications of a first-line metaraminol strategy should also be considered. A small Australian prospective observational study has shown the use of peripheral dilute norepinephrine to be a cheaper but equally safe and effective alternative to metaraminol for vasodilatory shock patients requiring low-dose vasopressors in the ICU.¹⁸ This finding warrants further investigation in larger trials.

Prolonged haemodynamic efficacy of metaraminol is not well described in intensive care patients. Previous experimental studies in shocked patients have shown that metaraminol reliably induces peripheral vasoconstriction and increases mean arterial pressure with either a slight reduction¹⁹ or no change in heart rate.⁷ Experimental animal studies have shown that kidney function is preserved with metaraminol infusion in septic shock models.²⁰ Our granular, hourly data on arterial pressures, heart rate, respiratory rate and urine output confirms these experimental findings in a large cohort of patients with vasodilatory shock. Up to 24 h after commencing metaraminol, mean arterial pressure was maintained despite weaning infusion doses, and heart rate and urine output remained stable. These findings support the safety and efficacy of metaraminol monotherapy and challenge hypotheses of tachyphylaxis with prolonged use previously reported in animal studies.⁶ Some caution needs to be applied to the interpretation of haemodynamic stability and urine output preservation, however, as this cohort had a relatively low severity of illness and short vasopressor duration.

Clinical implications and future directions

Metaraminol is an under-investigated vasopressor, and variation in clinical practice therefore remains common. This study confirms that metaraminol is a safe and effective vasopressor in low-risk patients but is underutilised in tertiary ICUs with conservative dosing thresholds. Further studies are required to confirm its comparative efficacy with norepinephrine, its favourable safety profile as a peripheral vasopressor agent, and cost evaluation with decreased central venous catheter utilisation. As such, future research directions should include larger prospective or registry-based evaluation of metaraminol usage trends and incidence of adverse events as well as prospective and randomised comparative trials of metaraminol and norepinephrine powered for patient-centred outcomes.

Strengths and limitations

This study has several strengths. It presents a large cohort of intensive care patients across two centres and, to our knowledge, is the largest study of critically ill patients receiving prolonged metaraminol infusion with hourly haemodynamic and physiologic data. We also had complete data collection on adjunctive vasopressor and inotrope infusions. Limitations of this study are its retrospective design and use of hourly haemodynamic variables and vasopressor doses, which might not account for minute-by-minute fluctuations. Our infusion data is limited to each patient’s ICU admission, and prior use of metaraminol in the emergency department or operating theatre was not considered. This might affect the generalisability of this study, particularly to those settings. We did not have recorded weight for all patients and have therefore not reported infusion doses in per kilogram units. Finally, we have been unable to report adverse events data (e.g. new onset atrial fibrillation, digital or bowel ischaemia, peripheral extravasation) for this cohort and are unable to provide clinician reasoning for conversion from metaraminol to norepinephrine for patients in this study.

Conclusions

Metaraminol is an infrequently utilised therapy in the ICU, most commonly reserved for unplanned patient admissions with a low severity of illness, and subsequent low risk of mortality. When commenced, metaraminol was almost always commenced as a first-line vasopressor for a short duration only. Dosing of metaraminol in the ICU is conservative and clinicians frequently transition to norepinephrine early despite the low doses infused. Metaraminol effectively maintains blood pressure with no associated tachycardia or significant drop in urine output and no clinical evidence of tachyphylaxis. In low-risk patients, metaraminol appears to be a safe and effective first-line vasopressor.

Supplemental Material

sj-docx-1-aic-10.1177_0310057X261453973 – Supplemental material for Characteristics and outcomes of intensive care patients receiving metaraminol infusion—a retrospective observational cohort study

Supplemental material, sj-docx-1-aic-10.1177_0310057X261453973 for Characteristics and outcomes of intensive care patients receiving metaraminol infusion—a retrospective observational cohort study by Rahul Costa-Pinto, Ary Serpa Neto, Andrew Udy, Linda Nguyen, Glenn Eastwood, Stephen Warrillow and Daryl Jones in Anaesthesia and Intensive Care

Supplemental Material

sj-docx-2-aic-10.1177_0310057X261453973 – Supplemental material for Characteristics and outcomes of intensive care patients receiving metaraminol infusion—a retrospective observational cohort study

Supplemental material, sj-docx-2-aic-10.1177_0310057X261453973 for Characteristics and outcomes of intensive care patients receiving metaraminol infusion—a retrospective observational cohort study by Rahul Costa-Pinto, Ary Serpa Neto, Andrew Udy, Linda Nguyen, Glenn Eastwood, Stephen Warrillow and Daryl Jones in Anaesthesia and Intensive Care

Supplemental Material

sj-docx-3-aic-10.1177_0310057X261453973 – Supplemental material for Characteristics and outcomes of intensive care patients receiving metaraminol infusion—a retrospective observational cohort study

Supplemental material, sj-docx-3-aic-10.1177_0310057X261453973 for Characteristics and outcomes of intensive care patients receiving metaraminol infusion—a retrospective observational cohort study by Rahul Costa-Pinto, Ary Serpa Neto, Andrew Udy, Linda Nguyen, Glenn Eastwood, Stephen Warrillow and Daryl Jones in Anaesthesia and Intensive Care

Supplemental Material

sj-docx-4-aic-10.1177_0310057X261453973 – Supplemental material for Characteristics and outcomes of intensive care patients receiving metaraminol infusion—a retrospective observational cohort study

Supplemental material, sj-docx-4-aic-10.1177_0310057X261453973 for Characteristics and outcomes of intensive care patients receiving metaraminol infusion—a retrospective observational cohort study by Rahul Costa-Pinto, Ary Serpa Neto, Andrew Udy, Linda Nguyen, Glenn Eastwood, Stephen Warrillow and Daryl Jones in Anaesthesia and Intensive Care

Footnotes

Acknowledgements

The authors would like to posthumously acknowledge the substantial contribution of Prof. Rinaldo Bellomo to this study’s conception and design.

Author contributions

Rahul Costa-Pinto: Conceptualization; Investigation; Methodology; Writing – original draft.

Ary Serpa Neto: Formal analysis; Investigation; Methodology; Writing – review & editing.

Andrew Udy: Conceptualization; Investigation; Methodology; Writing – review & editing.

Linda Nguyen: Investigation; Methodology; Writing – review & editing.

Glenn Eastwood: Conceptualization; Investigation; Methodology; Writing – review & editing.

Stephen Warrillow: Conceptualization; Investigation; Methodology; Writing – review & editing.

Daryl Jones: Conceptualization; Investigation; Methodology; Writing – review & editing.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Rahul Costa-Pinto

Supplemental material

Supplemental material for this article is available online.

References

Udy

Finnis

Jones

, et al. Incidence, patient characteristics, mode of drug delivery, and outcomes of septic shock patients treated with vasopressors in the arise trial. Shock 2019; 52: 400–407. doi:10.1097/SHK.0000000000001281

Grauslyte

Phull

Jovaisa

The use of metaraminol as a vasopressor in critically unwell patients: A narrative review and a survey of UK practice. J Cardiothorac Vasc Anesth 2022; 36: S21. doi:10.1053/j.jvca.2022.09.037

Liu

Gao

Zou

, et al. Randomised double-blind dose–response study of weight-adjusted infusions of metaraminol for preventing hypotension with combined spinal–epidural anaesthesia for elective Caesarean delivery in the supine position. Br J Anaesth 2022; 128: e20–e22. doi:10.1016/j.bja.2021.09.040

Evans

Rhodes

Alhazzani

, et al. Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021. Crit Care Med 2021; 49: e1063–e1143. doi:10.1097/CCM.0000000000005337

Sardaneh

Penm

Oliver

, et al. International pharmacy survey of peripheral vasopressor infusions in critical care (INFUSE). J Crit Care 2023; 78: 154376. doi:10.1016/j.crc.2023.154376

Harrison

Chidsey

Braunwald

Studies on the mechanism of action of metaraminol (Aramine). Ann Intern Med 1963; 59: 297–305. doi:10.7326/0003-4819-59-3-297

Natalini

Schivalocchi

Rosano

, et al. Norepinephrine and metaraminol in septic shock: A comparison of the hemodynamic effects. Intensive Care Med 2005; 31: 634–637. doi:10.1007/s00134-005-2607-3

Critchley

Conway

Hypotension during subarachnoid anaesthesia: Haemodynamic effects of colloid and metaraminol. Br J Anaesth 1996; 76: 734–736. doi:10.1093/bja/76.5.734

Sardaneh

Narayan

Penm

, et al. Efficacy and safety of metaraminol in critically ill patients with shock: A systematic review. J Pharm Pract Res 2022; 52: 83–93. doi:10.1002/jppr.1786

10.

Hussain

Jovaisa

Puthucheary

, et al. Peripherally administered vasopressors in critically ill adult patients: A survey of UK healthcare professional practices, attitudes and experiences. J Intensive Care Soc 2024; 25: 391–398. doi:10.1177/17511437241259443

11.

Sardaneh

Penm

Oliver

, et al. Pharmacoepidemiology of metaraminol in critically ill patients with shock in a tertiary care hospital. Aust Crit Care 2021; 34: 573–579. doi:10.1016/j.aucc.2021.01.002

12.

Zimsen

Quick

White

, et al. Prevalence and characteristics of metaraminol usage in a large intensive care patient cohort. A multicentre, retrospective, observational study. Crit Care Resusc 2025; 27: 100112. doi:10.1016/j.ccrj.2025.100112

13.

Safer Care Victoria. Metaraminol, https://www.safercare.vic.gov.au/sites/default/files/2018-12/Metaraminol_Emergency%20guideline_0.pdf (accessed 30 June 2025).

14.

Clark

Barton

Dean

, et al. Guidance for: The use of vasopressor agents by peripheral intravenous infusion in adult critical care patients. Intensive Care Soc 2022; 1: 1–16.

15.

Han

Zhou

Safety and efficacy of peripheral metaraminol infusion in patients with neurological conditions: A single-center retrospective observational study. Front Neurol 2024; 15: 1398827. doi:10.3389/fneur.2024.1398827

16.

Costa-Pinto

Neto

Matthewman

, et al. Dose equivalence for metaraminol and norepinephrine—a retrospective analysis. J Crit Care 2024; 80: 154430. doi:10.1016/j.jcrc.2023.154430

17.

Sardaneh

Goradia

Narayan

, et al. Dose equivalence between metaraminol and norepinephrine in critical care. Br J Clin Pharmacol 2022; 88: 303–310.

18.

Ruchti

Wibrow

Seet

, et al. A prospective comparison of peripheral metaraminol versus dilute norepinephrine in the intensive care unit. Anaesth Intensive Care 2021; 49: 144–146. doi:10.1177/0310057X20984794

19.

Malmcrona

Schröder

Werkö

. Hemodynamic effects of metaraminol: II. Patients with acute myocardial infarction. Am J Cardiol 1964; 13: 15–24. doi:10.1016/0002-9149(64)90217-6

20.

Bai

Tian

, et al. Effects of metaraminol and norepinephrine on hemodynamics and kidney function in a miniature pig model of septic shock. J Transl Int Med 2024; 12: 253–262. doi:10.2478/jtim-2023-0131

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