Desmopressin to reduce periprocedural bleeding and transfusion: a systematic review and meta-analysis

Wang, Carol; Lebedeva, Victoria; Yang, Jeffy; Anih, Joshua; Park, Lily J.; Paczkowski, Freeman; Roshanov, Pavel S.

doi:10.1186/s13741-023-00358-4

Perioperative Medicine

Table 1 Summary of findings for comparison of desmopressin to various comparator groups examining the hemostatic outcomes and potential adverse effects of desmopressin

From: Desmopressin to reduce periprocedural bleeding and transfusion: a systematic review and meta-analysis

Outcomes	No. of participants (studies)	Relative effect (95% CI)*	Absolute effect (95% CI)	p value for the main effect	p value for subgroup effect	Accrued IS/required IS; monitoring boundaries; interpretation‡	Quality of the evidence (GRADE)
Desmopressin vs placebo or usual care
Need for red blood cell transfusion¶	1944 (28)	RR 0.95 [0.86, 1.05]	21 fewer per 1000 (58 fewer to 21 more)	0.306		1944/2360; futility boundary crossed; 15% RRR unlikely; inconclusive regarding smaller effects	⨁⨁⨁◯ Moderate^a,^∏
Cardiac surgery	1460 (19)	RR 0.94 [0.83, 1.06]			0.887
Non-cardiac surgery	282 (7)	RR 1.01 [0.83, 1.24]
Interventional procedure	202 (2)	RR 0.85 [0.23, 3.07]
Baseline antiplatelet use	759 (9)	RR 0.95 [0.82, 1.09]			0.632
No baseline antiplatelet use	626 (9)	RR 0.89 [0.73, 1.08]			0.632
≥ 2012	325 (4)	RR 0.84 [0.49, 1.43]			0.923
< 2012	1619 (24)	RR 0.95 [0.85, 1.05]			0.923
Total volume of blood loss¶	2037 (35)	–-	0.40 SD lower (0.56 lower to 0.23 lower)	< 0.001		2037/593; monitoring boundaries crossed; conclusive for 15% reduction	⨁⨁◯◯ Low^a,b,^∏
Cardiac surgery	1581 (26)	SMD − 0.39 [− 0.59, − 0.18]			0.768
Non-cardiac surgery	456 (9)	SMD − 0.42 [− 0.64, − 0.21]			0.768
Baseline antiplatelet use	500 (8)	SMD − 0.31 [− 0.61, − 0.02]			0.676
No baseline antiplatelet use	572 (12)	SMD − 0.38 [− 0.59, − 0.17]			0.676
≥ 2012	317 (6)	SMD − 0.76 [− 1.19, − 0.32]			0.051
< 2012	1720 (29)	SMD − 0.32 [− 0.49, − 0.16]			0.051
Adult	1817 (31)	SMD − 0.43 [− 0.60, − 0.26]			0.262
Pediatric	220 (4)	SMD − 0.12 [− 0.46, 0.22]			0.262
Units of red blood cells transfused¶	1601 (26)	–-	0.55 fewer units (0.15 fewer to 0.94 fewer)	0.007		1601/1683; monitoring boundaries not crossed; inconclusive for 15% reduction	⨁⨁◯◯Low^a,b,^∏
Cardiac surgery	1025 (16)	MD − 0.71 [− 1.22, − 0.20]			0.306
Non-cardiac surgery	576 (10)	MD − 0.29 [− 0.92, 0.35]
Baseline antiplatelet use	305 (6)	MD − 0.45 [− 1.07, 0.16]			0.837
No baseline antiplatelet use	488 (8)	MD − 0.39 [− 0.68, − 0.10]
≥ 2012	123 (3)	MD − 1.76 [− 2.74, − 0.77]			0.003
< 2012	1478 (23)	MD − 0.34 [− 0.68, 0.00]
Adult	1566 (25)	MD − 0.53 [− 0.94, − 0.12]			0.720
Pediatric	35 (1)	MD − 0.90 [− 1.70, − 0.10]
Any bleeding¶	202 (2)	RR 0.45 [0.24, 0.84]	139 fewer per 1000 (192 fewer to 40 fewer)	0.012		202/3928; monitoring boundaries not crossed; inconclusive for 15% RRR	⨁⨁◯◯ Low^a,b,^∏
Reoperation due to bleeding	1831 (24)	RR 0.75 [0.47, 1.19]	11 fewer per 1000 (23 fewer to 8 more)	0.223		1831/28364; monitoring boundaries not crossed; inconclusive for 15% RRR	⨁⨁◯◯ Low^a,b,^∏
Cardiac surgery	1591 (21)	RR 0.74 [0.46, 1.19]			0.966
Non-cardiac surgery	30 (1)	RR 1.00 [0.02, 47.38]
Interventional procedure	210 (2)	RR 1.01 [0.06, 15.89]
Baseline antiplatelet use	722 (8)	RR 1.00 [0.47, 2.11]			0.816
No baseline antiplatelet use	504 (8)	RR 0.79 [0.23, 2.73]			0.816
≥ 2012	183 (2)	RR 0.67 [0.30, 1.50]			0.460
< 2012	1648 (22)	RR 0.80 [0.45, 1.43]			0.460
Adult	1741 (22)	RR 0.73 [0.45, 1.16]			0.753
Pediatric	90 (2)	RR 1.86 [0.16, 21.41]			0.753
Myocardial infarction	1866 (28)	RR 1.22 [0.75, 1.98]	5 more per 1000 (6 fewer to 22 more)	0.429		1866/57475; monitoring boundaries not crossed; inconclusive for 15% RRR	⨁⨁◯◯ Low^a,b,^∏
Cardiac surgery	1129 (17)	RR 1.40 [0.90, 2.47]			0.604
Non-cardiac surgery	535 (9)	RR 0.76 [0.27, 2.19]
Interventional procedure	202 (2)	RR 1.08 [0.75, 1.98]
Baseline antiplatelet use	373 (6)	RR 1.13 [0.39, 3.27]			0.970
No baseline antiplatelet use	796 (11)	RR 1.15 [0.60, 2.21]			0.970
≥ 2012	280 (4)	RR 1.03 [0.18, 5.82]			0.847
< 2012	1586 (24)	RR 1.23 [0.74, 2.05]			0.847
Stroke	1399 (20)	RR 1.31 [0.61, 2.84]	1 more per 1000 (2 fewer to 8 more)	0.487		1399/644159; monitoring boundaries not crossed; inconclusive for 15% RRR	⨁⨁◯◯ Low^a,b,^∏
Cardiac surgery	831 (12)	RR 1.51 [0.60, 3.85]			0.868
Non-cardiac surgery	406 (7)	RR 0.96 [0.22, 4.14]
Interventional procedure	162 (1)	RR 1.02 [0.02, 51.03]
Baseline antiplatelet use	223 (4)	RR 1.43 [0.28, 7.38]			0.785
No baseline antiplatelet use	479 (5)	RR 1.03 [0.20, 5.41]			0.785
≥ 2012	240 (3)	RR 0.99 [0.10, 9.35]			0.791
< 2012	1159 (17)	RR 1.37 [0.60, 3.10]			0.791
Hypotension	1321 (20)	RR 2.15 [1.36, 3.41]	29 more per 1000 (9 more to 60 more)	0.001		1321/49272; monitoring boundaries not crossed; inconclusive for 15% RRR	⨁⨁⨁◯ Moderate^a,^∏
Cardiac surgery	872 (14)	RR 2.39 [1.26, 4.53]			0.896
Non-cardiac surgery	247 (4)	RR 1.91 [0.96, 3.80]
Interventional procedure	202 (2)	RR 2.08 [0.18, 24.12]
Baseline antiplatelet use	511 (8)	RR 2.95 [1.20, 7.28]			0.506
No baseline antiplatelet use	581 (8)	RR 2.06 [1.18, 3.60]			0.506
≥ 2012	313 (4)	RR 1.56 [0.41, 5.95]			0.616
< 2012	1008 (16)	RR 2.25 [1.37, 3.67]			0.616
Adult	1231 (18)	RR 2.23 [1.40, 3.58]			0.443
Pediatric	90 (2)	RR 0.92 [0.10, 8.50]			0.443
Venous thromboembolism	1467 (21)	RR 0.81 [0.38, 1.76]	2 fewer per 1000 (5 fewer to 6 more)	0.597		1467/166587; monitoring boundaries not crossed; inconclusive for 15% RRR	⨁⨁◯◯ Low^a,b,^∏
Cardiac surgery	804 (11)	RR 0.71 [0.25, 2.02]			0.869
Non-cardiac surgery	461 (8)	RR 1.31 [0.32, 5.40]
Interventional procedure	202 (2)	RR 1.02 [0.02, 51.03]
Baseline antiplatelet use	311 (5)	RR 0.85 [0.18, 4.05]			0.949
No baseline antiplatelet use	577 (7)	RR 0.91 [0.223, 3.61]			0.949
≥ 2012	232 (3)	RR 0.49 [0.07, 3.72]			0.599
< 2012	1235 (18)	RR 0.88 [0.38, 2.04]			0.599
Hyponatremia (dichotomous)	254 (3)	RR 2.02 [0.53, 7.72]	16 more per 1000 (7 fewer to 105 more)	0.307		254/84520; monitoring boundaries not crossed; inconclusive for 15% RRR	⨁◯◯◯ Very low^a,b,^∏
Post-procedural serum sodium	103 (2)	–-	0.01 mmol/L lower (1.97 lower to 1.95 higher)	0.989		56/2103997; monitoring boundaries not crossed; inconclusive for 15% reduction	⨁◯◯◯ Very low^a,b,^∏
Desmopressin vs tranexamic acid
Need for red blood cell transfusion¶	135 (3)	RR 2.38 [1.06, 5.39]	330 more per 1000 with desmopressin (14 more to 1000 more)	0.037		135/9949; monitoring boundaries not crossed; inconclusive for 15% RRR	⨁⨁◯◯ Low^a,b,^∏
Total volume of blood loss¶	143 (3)	–-	391.7 mL more with desmopressin (93.3 less to 876.7 more)	0.113		143/749; monitoring boundary crossed; conclusive for 15% harm increase	⨁◯◯◯ Very low^a,b,^∏
Volume of red blood cell transfused¶	68 (2)	–-	1.25 units more with desmopressin (0.03 less to 2.52 more)	0.055		68/155; monitoring boundaries crossed; conclusive for 15% harm increase	⨁◯◯◯ Very low^a,b,^∏
Desmopressin vs Aprotinin
Reoperation due to bleeding	179 (2)	RR 1.36 [0.18, 10.29]	5 more per 1000 with desmopressin (11 fewer to 122 more)	0.765		179/94589; monitoring boundaries not crossed; inconclusive for 15% RRR	⨁◯◯◯ Very low^a,b,^∏
Myocardial infarction	179 (2)	RR 0.72 [0.05, 11.29]§	2 fewer per 1000 with desmopressin (6 fewer to 68 more)§	0.814		No events observed in control arm; unable to calculate	⨁◯◯◯ Very low^a,b,^∏
Stroke	179 (2)	RR 1.47 [0.13, 17.26]§	3 more per 1000 with desmopressin (6 fewer to 107 more)§	0.758		No events observed in control arm; unable to calculate	⨁◯◯◯ Very low^a,b,^∏
Venous thromboembolism	179 (2)	RR 0.39 [0.03, 4.62]	8 fewer per 1000 with desmopressin (13 fewer to 40 more)	0.458		179/61679; monitoring boundaries not crossed; inconclusive for 15% RRR	⨁◯◯◯ Very low^a,b,^∏

Abbreviations: CI confidence interval, IS information size, RR risk ratio, RRR relative risk reduction, SMD standardized mean difference, GRADE Grading of Recommendations, Assessment, Development, and Evaluations. The statistical analysis presented in this report was conducted with a predefined statistical power of 80% to detect the specified effects and associations
^*In cases where subgroups are presented, this value represents the effect within the specified subgroup
^†In cases where subgroups are presented, this value represents the interaction p value
^‡The information size was calculated based on an assumed relative risk reduction of 15% when desmopressin is administered during the periprocedural period for dichotomous outcomes. For continuous outcomes, these calculations were guided by empirical evidence on mean differences
^§The event rate in the aprotinin group was 0 across included studies for this outcome. To estimate the relative and absolute effect estimates, the event rate was assumed to be 0.5 in the aprotinin group
^¶The timing of ascertainment of transfusion requirements and blood loss varied from during the procedure to 96 h after (Desborough et al. 2017). Total blood loss was estimated by different techniques, including suction volume and drainage tube outputs. The volume of RBC transfusion was reported in either units or milliliters (subsequently converted to units assuming 300 mL per unit)
^aDowngrade one level for the risk of bias attributed to limitations in reporting of the randomization process and selection of the reported result
^bDowngrade one level for an inconsistency arising from unexplained statistical heterogeneity between studies
^cDowngrade two level due to imprecision arising from small sample size and confidence interval including no effect
^∏Relevant funnel plot for this outcome is found in Additional file 1: Figures S12, S13, S14, S15, S16, S17, S18, S19, S20, S21, S22, S23, S24, S25, S26, S27, S28, and S29

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ISSN: 2047-0525

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