Hypocalcemia and surgery for placenta accreta spectrum: Some concerns and considerations

Sir, In a recent publication in AOGS, Erfani et al1 concluded that “Intraoperative transfusion of ≥4 units RBCs [red blood cells] is predictive of the development of severe hypocalcemia (≤7 mg/dL) in placenta accreta spectrum (PAS) surgery and empiric placement of 1 g CaCl2 is recommended for every 4 units RBC transfused”. Levin and Rottenstreich2 question the validity of this because insufficient data are presented to support such a conclusion. We also have some concerns and considerations. First, Levin and Rottenstreich's criticism may be reasonable. The serum calcium level should be adjusted based on the serum albumin level: we usually employ Payne's equation.3 Adjusted calcium concentration (mg/dL) = serum calcium level (mg/dL) + (4 − serum albumin level [mg/dL]).3 Therefore, the adjusted calcium concentrations in Erfani et al's study were: Hypocalcemia group: 6.9 + (4 − 2.2) = 8.7 mg/dL; Control group: 8.8 + (4 − 3.4) = 9.4 mg/dL. This level of median-adjusted calcium concentration does not require replacement. Furthermore, alkalosis and hypermagnesemia usually cause hypocalcemia. The latter is present in patients receiving magnesium sulfate, which is sometimes administered to PAS patients to prevent uterine contractions. We wonder whether their study involved such patients. It is also unclear whether other features indicative of hypocalcemia were present, such as QT prolongation on electrocardiography or a prolonged prothrombin time/activated partial thromboplastin time. Second, from a practical viewpoint, Erfani et al's data do not support their recommendation for empiric CaCl2 replacement. Study group patients received a median of 4 units of RBC transfusion and median of 2 g of CaCl2, and still they showed hypocalcemia, meaning that empiric CaCl2 replacement (1 g CaCl2 for 4 units of RBC transfusion) may not ameliorate hypocalcemia. The third point regards the study target. Was PAS used as a study model because this condition frequently causes acute massive bleeding requiring RBC transfusion? Or, was PAS studied to formulate recommendations specific to PAS-surgery-related hypocalcemia? The study group showed a median of 1600 mL bleeding and required a median of 4 units of RBC transfusion. There are many other surgeries and conditions that require many more units of RBC transfusion: cardiovascular, liver, neuro-vascular surgery, or trauma care.4 Compared with these patients, PAS patients are fundamentally healthy, which may reduce the influence of underlying factors causing hypocalcemia. On the other hand, hemodilution or hypercoagulability-associated pregnancy may affect hypocalcemia. Comparing features of RBC transfusion-related hypocalcemia between PAS and non-pregnant individuals might have better characterized PAS-surgery-related hypocalcemia, providing useful data for physicians dealing with PAS. Erfani et al's data simply showed that hypocalcemia occurred in patients with PAS surgery if the RBC transfusion amount exceeded a certain level. This is common knowledge known to most physicians dealing with massive bleeding, not only those dealing with PAS. Erfani et al are experts in PAS surgery, and, so, we wish to learn from them about complications that are more specific to PAS surgery and how to prevent and manage them.