Elsevier

Journal of Critical Care

Volume 24, Issue 4, December 2009, Pages 551-555
Journal of Critical Care

Sedation
Comparison between dexmedetomidine and midazolam for sedation of eclampsia patients in the intensive care unit

https://doi.org/10.1016/j.jcrc.2009.02.001Get rights and content

Abstract

Purpose

This study compares the effectiveness of midazolam and dexmedetomidine for the sedation of eclampsia patients admitted to our intensive care unit (ICU).

Patients and Methods

Forty women with eclampsia requiring termination of pregnancy by caesarean delivery were randomized in to 2 groups of 20 to receive either midazolam or dexmedetomidine. The midazolam group received a loading dose of 0.05 mg/kg followed by an infusion of 0.1 mg kg−1 h−1. The dexmedetomidine group loading dose was 1 μg/kg per 20 minutes, followed by continuous infusion at 0.7 μg kg−1 h−1. Heart rate, blood pressure, Ramsey sedation score, antihypertensive need, convulsion fits, and duration in ICU were monitored and recorded all through the ICU stay.

Results

Dexmedetomidine markedly reduced heart rates for the first 24 hours (P < .05) compared with midazolam, but there were no differences at 48 and 72 hours. Mean arterial blood pressures were similar in the 2 groups (P > .05), although in the dexmedetomidine group, it was lower at 5, 6, 12, and 24 hours compared with the first 4 hours (P < .05). Moreover, fewer patients given dexmedetomidine required nitroglycerine and nitroprusside (P < .05). The duration of ICU stay was less in the dexmedetomidine group, 45.5 hours (range, 15-118 hours), than in the midazolam group, 83 hours (minimum-maximum, 15-312 hours).

Conclusion

Dexmedetomidine sedation in eclampsia patients is effective in reducing the demand for antihypertensive medicine and duration of ICU stay.

Introduction

Preeclampsia is characterized by hypertension diagnosed after 20 weeks gestation plus proteinuria. In severe cases, the diastolic blood pressure is 110 mm Hg or more, there is a persistent proteinuria of 2 or more, and any of the following can be present: headaches, visual disturbances, upper abdominal pain, oliguria, increased serum creatinine, thrombocytopenia, increased liver enzymes, fetal growth retardation, and pulmonary edema. Eclampsia is the new onset of seizures before, during, or after labor, which is not attributable to other causes, in a woman with preeclampsia. Eclampsia, a complication of pregnancy characterized by seizures and accompanied by severe hypertension, brain and lung edema, aspiration pneumonia, and acute renal failure, remains a major cause of maternal morbidity and mortality in both developed and developing countries. Proteinuria and acute respiratory distress syndrome can also follow [1].

The main goals of treatment are to stabilize the patient; control derangements of the cardiovascular, hematological, renal, pulmonary, and central nervous systems; and prevent potential future problems [2]. It is critical for both mother and baby that new seizures be effectively controlled; they are usually treated with magnesium sulfate, intramuscularly or intravenously, but may still occur, exacerbating maternal morbidity and mortality [1].

Several anticonvulsant drugs have been tried. Midazolam is a fast-acting benzodiazepine with a short elimination half-life; has powerful anxiolytic, amnesic, hypnotic, anticonvulsant, skeletal muscle relaxant, and sedative properties; and has been used for sedation in the intensive care unit (ICU) for many years. Its use has been proposed for the treatment of eclampsia. Midazolam undergoes extensive oxidation in the liver via the cytochrome P450 enzyme system to form water-soluble hydroxylated metabolites, which are excreted in urine. However, the primary metabolite, namely, 1-hydroxymethylmidazolam, has mild central nervous system depressant activity and may accumulate in the critically ill patient, especially in the case of kidney failure [3], [4], [5].

Dexmedetomidine is a centrally acting α2-agonist with sedative and analgesic properties; it is similar to clonidine but has much greater α2 to α1 binding affinity. The sedative properties are facilitated through the locus coeruleus site in the central nervous system, and the analgesic effects may occur via activation of the α2-receptors by accentuating the action of opioids. After extensive metabolism in the liver, dexmedetomidine is eliminated as methyl and glucuronide conjugates, mainly (95%) via renal excretion [6].

Dexmedetomidine used in intensive care as a sedative without respiratory depressive effects has analgesic properties and controls stress, anxiety, and pain [7].

In this clinical study, we compare dexmedetomidine and midazolam for sedation in eclampsia patients with regard to their effectiveness, hemodynamic characteristics, and ICU discharge time.

Section snippets

Patients and methods

This is a prospective, randomized, and controlled study. After obtaining ethic committee approval from Erciyes University Hospital, patients' first-degree relatives were informed about the study, and their written consent was taken. Forty patients whose pregnancies were terminated via caesarean delivery because of eclampsia and who needed ventilatory support were included in the present study. All patients who had chronic hypertension; cardiac, neurological, hepatic, renal, or endocrinal

Results

There were no statistically significant differences between the GrM and GrD with respect to operation time, age, weight, or height of the patients (P > .05; Table 2).

Dexmedetomidine reduced heart rates at 1, 2, 3, 4, 5, 6, 12, and 24 hours much more than midazolam did (P < .05; Fig. 1). The difference in heart rates disappeared at 48 and 72 hours.

Mean arterial pressure was similar in the 2 groups initially but was lower in the GrD at 5, 6, 12, and 24 hours (P < .05; Fig. 2).

The need for

Discussion

An ideal ICU sedation agent should rapidly act and have analgesic and sedative properties to prevent anxiety and unpleasant recall. It should generate only mild cognitive impairment, allowing easy communication between physician and patient. Moreover, it should not accumulate in the body. It should not demonstrate tachyphylaxis or cause withdrawal symptoms when its use is terminated [8]. In our study, dexmedetomidine allowed a shorter ICU stay and reduced antihypertensive use compared with

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