补充大剂量维生素D对结直肠手术患者围手术期维生素D水平的影响

　　低维生素D水平与多种围手术期不良结局，如感染、心血管事件、住院死亡率等密切相关，而优化维生素D水平的策略仍然比较欠缺。

　　为了探讨口服大剂量胆钙化（甾）醇（维生素D3）对围手术期患者血清维生素D的影响，麻省总医院（马萨诸塞州综合医院）入组60例等待结直肠手术的患者进行随机安慰剂对照研究，两组分别在术前5～7天给予大剂量维生素D3（100000IU）和安慰剂，并在围手术期监测相关血液指标。

　　结果发现大剂量维生素D3组能显著改善患者围手术期血维生素D水平，降低术后促炎因子水平，增加内源性抗菌肽（一种参与固有免疫的小分子多肽，具有广谱抗菌活性，构成宿主防御细菌、真菌等入侵的重要分子屏障）的产生，并且无不良反应发生。

JPEN J Parenter Enteral Nutr. 2016;40:121-3.

Effect of High-Dose Cholecalciferol Supplementation on Perioperative Vitamin D Status in Colorectal Surgery Patients: A Randomized Placebo-Controlled Pilot Trial.

Quraishi SA, McCarthy CM, Needleman J, Herzog E, Berger D, Camargo CA.

Massachusetts General Hospital, Boston, MA, USA.

PURPOSE: Low vitamin D status is associated with various undesirable perioperative outcomes, such as healthcare-associated infections, cardiovascular events, and in-hospital mortality. However, very little is known about strategies to optimize perioperative vitamin D status. Therefore, our goal was to conduct a randomized placebo-controlled trial to determine the effect of high-dose cholecalciferol (vitamin D3) supplementation on perioperative vitamin D status in patients scheduled for elective colorectal surgery.

METHODS: The experimental protocol was registered on ClinicalTrials.gov (NCT01689779). We planned on recruiting a total of 80 patients with an interim analysis once 60 patients had completed the study. Patients scheduled for elective colorectal surgery received either a single oral dose of cholecalciferol (100,000 IU) or a matched placebo 5-7 days before surgery. Blood samples were assessed at baseline, on the day of surgery, on postoperative day 1, and during follow-up on postoperative days 12-14 for (1) 25-hydroxyvitamin D (25OHD), (2) albumin and vitamin D binding protein to calculate bioavailable 25OHD (b25OHD), (3) the endogenous antimicrobial peptide cathelicidin (LL-37), and (4) levels of inflammatory markers high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), and IL-10. Percentage change (Δ) in biomarkers relative to baseline, day of surgery, postoperative day 1, and postoperative days 12-14 were compared between groups via 2-way repeated-measures analysis of variance tests. Simple linear regression modeling was used to test the relationship between Δ25OHD/Δb25OHD and ΔLL-37.

RESULTS: Demographic and clinical information related to the placebo (n = 32) and cholecalciferol (n = 28) groups at interim analysis is shown in Table 9-1. All biomarkers were similar between groups at baseline. Changes in 25OHD and b25OHD over time are shown in Figure 9-1. Analysis of variance testing demonstrated a difference in Δ25OHD, Δb25OHD, and ΔLL-37 levels between groups (F = 16.7, P = .001; F = 7.7, P = .007; and F = 2.08, P = .005, respectively) and over time (F = 66.5, P < .001; F = 3.2, P = .04; and F = 10.47, P = .001, respectively). Δb25OHD (r = 0.42, P = .01) but not Δ25OHD (r = 0.32, P = .11) was found to correlate with ΔLL-37. ΔhsCRP and ΔIL-6 were not different between groups (F = 0.01, P = .9; F = 1.05, P = .41, respectively) but were different over time (F = 15, P < .001; F = 11.44, P < .001). However, ΔIL-10 was different between groups (F = 1.66, P = .02) and over time (F = 7.17, P = .001). There were no adverse effects related to cholecalciferol supplementation noted throughout the duration of the study. The trial was closed following the interim analysis due to a significant improvement in vitamin D status in the cholecalciferol group versus the placebo group. Further enrollment was not expected to materially change these results.

Figure 9-1. Data in the figures represent percentage (%) change in vitamin D status (1A, 1B) and inflammation (1C) as compared with baseline. In the placebo group, a postoperative drop in 25OHD is accompanied by a drop in b25OHD. In supplemented patients, postoperative b25OHD is maintained despite an apparent drop in 25OHD. 25OHD, 25-hydroxyvitamin D; b25OHD, bioavailable 25OHD; DOS, date of surgery; hsCRP, high-sensitivity C-reactive protein; POD1, postoperative day 1; POSTOP, postoperative days 12-14.

CONCLUSIONS: In our cohort of patients, a single dose of cholecalciferol (100,000 IU) given 5-7 days before elective colorectal surgery was safe and resulted in significant improvement in perioperative vitamin D status. Moreover, our data suggest that preoperative vitamin D supplementation may influence postoperative cytokine levels and influence expression of endogenous antimicrobial peptides. Future trials are needed to build on our findings and to determine whether preoperative vitamin D status optimization can influence important clinical outcomes, such as postoperative complications, length of stay, and mortality.

FINANCIAL SUPPORT: Massachusetts General Hospital.