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SYSTEMATIC REVIEW
Year : 2022 | Volume
: 8
| Issue : 3 | Page : 144-151
Effect of labetalol for treating patients with pregnancy-induced hypertension: A systematic review
Punyatoya Bej1, Sambhunath Das2
1 Associate Professor, Department of Community Medicine, Rama Medical College and Research Centre, Hapur, Uttar Pradesh, India
2 Professor, Department of Cardiac Anaesthesia, All India Institute of Medical Sciences, New Delhi, India
Correspondence Address:
Punyatoya Bej
Associate Professor, Department of Community Medicine, Rama Medical College and Research Centre, Hapur, Uttar Pradesh
India
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/jpcs.jpcs_69_22
Pregnancy-induced hypertension (PIH) is one of the main causes of maternal mortality. Many first- and second-line drugs are available to treat the condition. Labetalol lowers blood pressure by blocking both α and β adrenergic receptors. It preserves uteroplacental blood flow efficiently. A systemic review was carried out to find the efficacy and safety of labetalol in the treatment of PIH. Three thousand twenty-six studies were retrieved in 20 years. Finally, 28 studies were selected after applying the review criteria. Twenty-three studies detected that labetalol had superior or similar action compared to other drugs in controlling hypertension in patients with preeclampsia and eclampsia. The systematic review concluded that labetalol is a safe, effective, first-choice of drug with few side effects in treating PIH.
Keywords: Eclampsia, fetal outcome, labetalol, maternal outcome, nifedipine, preeclampsia, pregnancy-induced hypertension
Pregnancy-induced hypertension (PIH) is one of the main reasons for maternal morbidity and mortality in pregnancy. Many patients are admitted in an emergency. Treatment of PIH disorders such as preeclampsia and eclampsia is a challenging task.[1],[2] Proper treatment is essential to choose the best antihypertensive agent.
Many first and second-line drugs are available. Labetalol is one of them. Labetalol reduces blood pressure (BP) by blocking α and β adrenergic receptors. It can better preserve uteroplacental circulation as compared to other β blockers.[1] The onset of action is faster in labetalol compared to methyldopa.[1] PIH drug treatment should be titrated to prevent sudden drop in BP and the drug should not have any adverse effect on the fetus.[3],[4]
A literature search in peer-reviewed journals found a small number of systematic reviews and meta-analysis related to the use of labetalol in PIH. The present systematic review was planned to detect the effect of labetalol compared to all other antihypertensive drugs used in clinical practice to treat PIH in patients with preeclampsia and eclampsia for more than 20 years; and which antihypertensive drug is safer with ease of administration.
MethodologyResearch question
The systematic review was planned to detect the effect of labetalol in comparison to other antihypertensive drugs in reducing PIH in preeclampsia and eclampsia patients which antihypertensive medication is safer with ease of administering.
Research protocol
We searched for original articles detecting the efficacy of labetalol in PIH patients. Studies of comparison between labetalol and hydralazine, methyldopa, nifedipine, and any other antihypertensive drugs were included in the review. Original full-text articles were retrieved. Articles of review, systemic review, meta-analysis, case reports, and editorial and qualitative studies were excluded.
Literature search
The literature search on the effect of labetalol on preeclampsia and eclampsia was conducted from PubMed and Google Scholar databases over the last 20 years. The literature search was conducted by two independent reviewers. The keywords used for the literature search were labetalol, PIH, original studies, and clinical trials. Articles with other antihypertensive drugs that were compared with labetalol for PIH were considered. The maternal, fetal, and renal outcomes and other side effects were studied. The effects on BP control with these drugs also were compared. The systematic review methodology according to the recommendations for systematic review and meta-analyses (PRISMA) guideline is mentioned in [Figure 1].
Data interpretation
The efficacy and safety of labetalol were assessed and represented in tabular form. The number of articles showing labetalol as the first choice or superior among studies was noted. Studies showing similar or inferior results or results between labetalol and others were also highlighted. The final clinical utility of labetalol for controlling PIH was derived.
ResultsA total of 28 full-text articles were finalized for systemic review. The articles were mentioned in tabular form with the respective findings [Table 1].
From 28 studies, 11 (39.2%) studies reported that labetalol was the best and first-line drug for the treatment of preeclampsia and eclampsia as compared to nifedipine, hydralazine, methyldopa, and magnesium sulfate. In 3 (10.7%) studies, it is depicted that the efficacy of hydralazine and labetalol was similar to control the acute rise in BP.[6],[27] In 7 (25%) studies, nifedipine and labetalol were proven to be similarly effective in reducing BP in preeclampsia and eclampsia patients. Labetalol and methyldopa were comparable in lowering BP among preeclampsia and eclampsia patients in two studies. Hence, in 12 studies, labetalol had a similar effect compared to others. In total labetalol was an effective drug to treat PIH in 23 (82.1%) studies out of 28. Labetalol was proved inferior in 5 (17.8%) articles (3 studies to oral nifedipine, 1 study to methyldopa, and 1 study to nicardipine) [Figure 2].
Figure 2: Efficacy of labetalol in treating hypertension during PIH. PIH: Pregnancy-induced hypertension.Labetalol was beneficial in patients with reflex tachycardia, myocardial infarction, and renal diseases associated with PIH. Side effect such as fetal bradycardia was observed with labetalol in one study.[33] Labetalol was contraindicated in severe asthma patients.
DiscussionSome women develop high BP during pregnancy only, which returns to normal after the birth of the baby.[2] This is called PIH or gestational hypertension (HTN). PIH may be associated with preeclampsia and eclampsia. Eclampsia manifests with HTN, proteinuria, visual disturbance, convulsion, preterm delivery, high incidence of intrauterine death, and maternal multi-organ failure.[2]
A group of medications is available for the treatment of PIH during preeclampsia and eclampsia.[1] The effectiveness and safety profile of the drugs need to be evaluated for proper clinical use in PIH. Rapid control of PIH is the prime importance for the survival of the mother and fetus.[34] The first-line antihypertensive drug must be chosen for the rapid control of high BP in preeclampsia and eclampsia cases. The oral dose of labetalol is 100 mg two times a day.[35] The intravenous dose of labetalol is 20 mg starting over 2 min. Additional 40 or 80 mg may be supplemented every 10 min as per the need up to a maximum of 300 mg.[35] Labetalol also can be started at 1–2 mg/min intravenously.[2]
This systematic review noticed that 23 (82.1%) out of 28 studies were in favor of labetalol as the first choice of drug to control PIH. Labetalol was better compared to all other drugs. Eleven studies had detected superior and 12 articles proved similar efficacy and safety between labetalol and other drugs like hydralazine, nifedipine, and methyldopa. Labetalol use was safe for the baby and mother.[36] Labetalol did not cause miscarriage. It can also better preserve uteroplacental circulation in comparison to the rest of the beta blockers. It acts faster compared to methyldopa. In a randomized control clinical trial, Molvi et al. compared labetalol with either methyldopa or nifedipine; have proved labetalol to be safe during pregnancy.[36] Few studies depicted that aspirin can be used in preeclampsia and eclampsia patients to prevent thrombosis.[37]
Labetalol has some side effects and limitations which were observed during the studies and have to be in consideration. Labetalol is contraindicated in asthmatic patients, atrioventricular block (2nd and 3rd degree), and in uncontrolled heart failure with bradycardia.[33] A few side effects are blurred vision, sweating, difficulty in breathing, dizziness, lightheadedness when rising from lying down or sitting posture, dyspnea, swelling of limbs, chest rigidity, and wheezing. Labetalol can mask the early warning symptoms of hypoglycemia, like tremors and tachycardia. Therefore, patients taking insulin and oral hypoglycemic drugs may need to increase the dose to prevent accidental hypoglycemia. Labetalol may produce liver toxicity. It is imperative to recognize this side effect of hemolysis, elevated liver enzymes, and low platelet count syndrome.[38] The liver function derangement due to labetalol gradually subsides after discontinuation of treatment.[39]
The prompt and effective control of PIH will reduce the development of congestive heart failure, acute myocardial ischemia, intracranial hemorrhage, stroke, and renal injury. A recent guideline by the American College of Obstetrics and Gynecology has published recommendations for preeclampsia and eclampsia patients with PIH.[40] A systolic BP of ≥160 mmHg and diastolic BP of ≥110 mmHg should be diagnosed with PIH. It recommends aspirin in a dose of 81 mg/day from 16 weeks of gestation to the delivery of newborn. The recommended drugs for the control of HTN are labetalol, hydralazine, and oral nifedipine. Magnesium sulfate should be started with the development of convulsions in eclampsia and preeclampsia. Nonsteroidal anti-inflammatory drugs should be advised as analgesics rather than opioids to avoid respiratory depression. Anti-hypertensive drug treatment should be started as soon as possible once PIH, preeclampsia, eclampsia, and convulsion are observed in a patient. Delivery is recommended when gestational HTN, preeclampsia, and maternal adverse events are diagnosed at or after 34 weeks.
An Internet search found 5 systematic reviews and meta-analyses on the antihypertensive treatment for PIH.[41],[42],[43],[44],[45] The outcome is in favor of nifedipine, labetalol, and hydralazine for effective control of BP. Two meta-analyses showed, nifedipine as the first line of antihypertensive agent.[43],[44] One meta-analysis detected, labetalol reduced proteinuria and fetal as well as neonatal death.[41] One meta-analysis found hydralazine treatment had more tachycardia, and higher maternal and fetal morbidity.[42] Ketanserin, diazoxide, and dihydralazine had more adverse effects and were unsafe for use.[43],[46] A Cochrane review by Duley et al. observed that the antihypertensive therapy for PIH was based on the clinician's experience with the drug and the availability at the hospital.[46] Labetalol, hydralazine, and nifedipine were commonly used drugs for the control of HTN. Nimodipine and magnesium were used in patients of PIH with associated convulsions.[46]
Despite these side effects, labetalol proved to be more effective for the successful control of HTN due to PIH. The benefits outweigh the minor risks. Labetalol is safe to be used for the mother, fetus, and newborn with negligible adverse outcomes. The systemic review recommends that labetalol may be the preferred and first-line drug of choice compared with nifedipine, methyldopa, hydralazine, nicardipine, and magnesium in the management of PIH.
Limitations
Data from all types of prospective studies were included with a heterogeneous design of studies in the present systemic review. All the patients had not adopted the intention to treat principle. The randomized controlled trial were both open and double-blinded studies. Despite the limitations, the study included a large number of studies over 20 years to derive an evidence based practice.
ConclusionLabetalol is a more effective and safe drug in controlling HTN among preeclampsia and eclampsia patients. It has a faster onset of action both in oral and intravenous routes as compared to other available drugs. The prevalence of side effects with labetalol is less. Hence, labetalol may be chosen as the first choice drug in managing PIH in clinical practice.
Ethics clearance
Not applicable.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
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