2022 Volume 10 Issue 1 Pages 4-7
Aim: This study aimed to clarify whether calcium administration has a therapeutic effect against cardiac arrest resulting from magnesium toxicity in pregnant or puerperal women, and to determine whether the body of evidence published to date suggests the need for a systematic review.
Methods: This review was guided by a specific methodological framework and Preferred Reporting Items for Systematic reviews and Meta-Analysis extension for Scoping Reviews. Literature published up to September 24, 2020 was searched using the Medline database. Eligible articles included peer-reviewed studies in humans that prospectively or retrospectively evaluated the effects of calcium therapy on clinical outcomes and had an English abstract. Two reviewers independently screened the search results and extracted data from analyzed studies.
Results: Nineteen references were screened, and nine studies were analyzed. Five studies described maternal cardiac arrest or hypotension due to hypermagnesemia, and two studies described cardiac arrest in non-pregnant women due to hypermagnesemia. The remaining two articles were guidelines that described calcium administration for hypermagnesemia. We did not identify high-quality or large-sample studies which are needed to perform a systematic review.
Conclusions: The identified studies were insufficient to change existing recommendations. However, calcium administration may be considered for cardiac arrest associated with hypermagnesemia if ready to be performed during cardiopulmonary resuscitation.
In 2018, the Japan Resuscitation Council (JRC) launched the Maternal Resuscitation Task Force to revise the 2015 JRC resuscitation guidelines. The Task Force used the Population, Intervention, Comparison, and Outcome (PICO) method to evaluate calcium therapy for maternal cardiac arrest suspected to have resulted from hypermagnesemia because magnesium toxicity is one of the most common etiologies of maternal cardiac arrest and mortality.1) Intravenous (i.v.) calcium administration is recommended for the treatment of hypermagnesemia,2,3) and has been suggested as an option in the 2010 American Heart Association (AHA) guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiovascular care (ECC) and the European Resuscitation Council (ERC) Guidelines for resuscitation 2015.4,5) However, the effects of this intervention on clinical outcomes are largely unexplored. Therefore, we conducted a scoping review, including an analysis of evidence from non-pregnant women, with the aim of (i) determining whether research to date has focused on cardiac arrest due to magnesium toxicity in pregnant or puerperal women, and (ii) identifying evidence related to calcium administration in this unique context to determine whether the body of evidence published to date suggests the need for a systematic review.
The methodological steps of the systematic literature search and review were based on the framework proposed by Arksey and O’Malley. The reporting of results followed the Preferred Reporting Items for Systematic reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR).6,7)
Search strategyA comprehensive computer search of the literature on calcium administration for maternal cardiac arrest was conducted using the Medline database from inception to September 24, 2020. The following search terms were used: ((pregnancy or pregnancies or gravid or gravidity or gestating or parturient or peripartum or expecting mother or child-bearing or maternal or obstetric) AND (cardiac arrest, cardiac arrests, cardiopulmonary arrest, cardiopulmonary arrests, cardio-pulmonary arrest, cardio-pulmonary arrests, asystole, heart failure, heart arrest, heart arrests, heart attack, heart stoppage, cardiovascular arrest, cardiovascular arrests, advanced cardiac life support, advanced life support) AND (magnesium or magnesium sulfate or high-magnesium or magnesium therapy or hypermagnesemia, magnesium concentration, magnesium toxicity, magnesium overdose)) AND (calcium or calcium therapy, calcium-containing calcium carbonate, calcium gluconate, calcium administration, calcium infusion). We also added references identified by manual searches if they were not included in the search results. The literature search using the aforementioned search terms was performed separately by two reviewers, and the results were reassessed until the results from the two reviewers matched.
Inclusion and exclusion criteriaStudies were considered eligible for inclusion if they were peer-reviewed human studies that prospectively or retrospectively evaluated the effects of calcium therapy on clinical outcomes (e.g., return of spontaneous circulation and survival to a defined time point). Unpublished studies and studies published in abstract form only, those written in other languages without English abstracts, manikin studies, and animal studies were excluded.
There were 19 hits from the database search, to which we added eight additional publications identified in a manual search. Fourteen publications were excluded based on their titles and abstracts, and 13 full-text articles were evaluated for eligibility. Of these, nine were considered eligible for inclusion (Figure 1). Information regarding the nine articles is summarized in Table 1.
Search strategy flowchart
| Article | Study design | Country | Sample size | Comments on hypermagnesemia and calcium administration |
|---|---|---|---|---|
| Swartjes JM, et al. Eur J Obstet Gynecol Reprod Biol. 1992. | Case report | The Netherlands | 1 | Maternal cardiac arrest due to hypermagnesemia; 1 g i.v. calcium gluconate given two times after ROSC. |
| McDonnell NJ. Br J Anesth. 2009. | Case report | Australia | 1 | (Case 2) Maternal cardiac arrest due to hypermagnesemia. ROSC after PMCD without calcium administration. |
| Qureshi TI, et al. Ann Emerg Med. 1996. | Case report | USA | 1 | Cardiac arrest due to hypermagnesemia in a non-pregnant woman; 1.1 g i.v. calcium gluceptate administered two times after ROSC, and later she was extubated. |
| Mordes JP et al. Ann Intern Med. 1975. | Case report | USA | 1 | Cardiac arrest due to hypermagnesemia in a non-pregnant woman; 1 g bolus of calcium chloride was administered two times after ROSC, and her blood pressure rose transiently. |
| Bohman VR, et al. Obstet Gynecol. 1990. | Case report | USA | 1 | Magnesium infusion was discontinued and 1 g of calcium chloride i.v. injection over 30 seconds improved respiratory arrest due to hypermagnesemia in a pregnant woman with preeclampsia. |
| Cao Z, et al. Clin Chim Acta. 1999. | Case report | USA | 1 | Calcium gluconate, 10 ml (2.33 mmol of calcium), via i.v. administration improved respiratory arrest due to hypermagnesemia in a pregnant woman with preterm labor. |
| McDonnell NJ, et al. Int J Obstet Anesth. 2010. | Case report | Australia | 1 | Bolus administrations of 10 ml of i.v. 10% calcium gluconate two times improved respiratory depression due to hypermagnesemia in a pregnant woman with preeclampsia and HELLP syndrome. |
| Vanden Hoek TL, et al. Circulation. 2010. | Guideline | USA | N.A. | Empirical use of calcium (calcium chloride [10%] 5–10 ml OR calcium gluconate [10%] 15–30 ml i.v. over 2–5 minutes) may be considered when hypermagnesemia is suspected as the cause of cardiac arrest (Class IIb, LOE C). |
| Truhlár A, et al. Resuscitation. 2015. | Guideline | Czech Republic | N.A. | Calcium chloride 10% 5–10 ml, repeated if necessary, is considered as a resuscitative measure for patients with maternal cardiac arrest or respiratory circulatory failure due to magnesium poisoning (magnesium >1.75 mmol/L). |
i.v., intravenous; ROSC, return of spontaneous circulation; PMCD, perimortem cesarean delivery; USA, United States of America; MgSO4, magnesium sulfate; HELLP, hemolysis elevated liver enzymes and low platelet count; NA, not applicable.
No randomized or non-randomized large studies were identified. Two case reports described maternal cardiac arrest due to magnesium toxicity where calcium was not administered during CPR.8,9) Two additional case reports described cardiac arrest due to hypermagnesemia in non-pregnant women.10,11) Both respiratory and circulatory status improved after calcium administration, although calcium was not administered during CPR in either case. There were three case reports on effective treatment with calcium for maternal respiratory depression or arrest and hypotension associated with hypermagnesemia.12,13,14) Two guidelines from the AHA and ERC stated that calcium administration for cardiac arrest due to hypermagnesemia was a treatment option.4,5)
This scoping review did not identify high-quality or large-sample studies on whether calcium administration during CPR is a valid treatment approach, nor did we identify sufficient new evidence to prompt a systematic review.
Information from the identified studies was considered insufficient to change existing recommendations. However, i.v. calcium administration can be used to temporarily antagonize the cardiovascular and neuromuscular effects of magnesium,15) which may be beneficial when hypermagnesemia is suspected as a cause of cardiac arrest and i.v. access is readily available. Therefore, if prepared and ready at the time of standard CPR, calcium administration (e.g., i.v. calcium gluconate or chloride) may be considered for cardiac arrest together with magnesium therapy, given that magnesium sulfate is widely used in obstetric care for patients with hypertensive disorders of pregnancy/eclampsia/preterm labor with a risk of an iatrogenic overdose.
The recommended method of calcium administration described in the studies was similar,2,3,4,5) i.e., i.v. injection of 1 g calcium gluconate or chloride (equivalent to 10 ml of 10% preparations). However, repeated doses may be needed to achieve the expected effect during CPR due to hypoperfusion rather than spontaneous circulation.16)
Knowledge GapsThere were several gaps in the published literature, the most notable of which were: the lack of high-level evidence related to calcium administration for hypermagnesemia during CPR and a failure to account for the appropriate timing and dose of administration for resuscitative measures, the possibility of delayed standard resuscitation due to calcium administration during CPR, and possible adverse events caused by hypercalcemia due to calcium administration.
This scoping review did not identify high-quality or large-sample studies on whether calcium administration during CPR is a valid treatment approach, nor did we identify sufficient new evidence to prompt a systematic review. Calcium administration may be considered for cardiac arrest associated with hypermagnesemia if ready to be performed during CPR.
The authors thank the following members of the Maternal group of the Japan Resuscitation Council: Dr. Shinji Baba, Dr. Naosuke Enomoto, Dr. Yuki Hosokawa, Dr. Rie Kato, Dr. Takahide Maenaka, Dr. Eishin Nakamura, Dr. Masafumi Nii, Dr. Shinji Takahashi, Dr. Makoto Tsuji, Dr. Yoshihiro Yamahata, and Dr. Tomoyuki Yamashita. The authors also thank the following members of the Japan Resuscitation Council: Dr. Mayuki Aibiki, Dr. Tetsuo Hatanaka, Dr. Shigeharu Hosono, Dr. Takanari Ikeyama, Dr. Tetsuya Isayama, Dr. Taku Iwami, Dr. Yasuhiro Kuroda, Dr. Tasuku Matsuyama, Dr. Masao Nagayama, Dr. Chika Nishiyama, Dr. Hiroshi Nonogi, Dr. Tetsuya Sakamoto, and Dr. Naoki Shimizu.
The authors report no conflict of interest
None.
