Electronic Supplementary Material N

Electronic Supplementary Material n. 2.

Article: Diagnostic accuracy of passive leg raising for prediction of fluid responsiveness in adults: systematic review and meta analysis of clinical studies. Journal: Intensive Care Medicine Authors: Cavallaro F, Sandroni C, Marano C, La Torre G, De Waure C, Mannocci A, Bello G, Maviglia R, Antonelli M Corresponding Author: Fabio Cavallaro, MD. Registrar, Catholic University School of Medicine, Intensive Care Unit Mail to: Università Cattolica del S. Cuore di Roma Policlinico “A. Gemelli” Largo A. Gemelli 8 00168 Rome, Italy Email to: [email protected] Phone work: +39063015-4507 (-4490 / -4889) Phone home: +390645448652 Mobile: +393385969590 Fax: +390697656462 Pooling analysis of sensitivity, specificity, likelihood ratio and diagnostic odds ratio for PLR- induced changes in cardiac output (PLR-cCO).

Summary Sensitivity

Study | Sen [95% Conf. Iterval.] TP/(TP+FN) TN/(TN+FP) ------Lafanechere 2006(18) | 0,900 0,555 - 0,997 9/10 10/12 Monnet 2006 (19) | 0,973 0,858 - 0,999 36/37 32/34 Lamia 2007 (20) | 0,769 0,462 - 0,950 10/13 11/11 Maizel 2007 (21) | 0,941 0,713 - 0,999 16/17 14/17 Thiel 2009 (13) | 0,818 0,691 - 0,909 45/55 44/47 Monnet 2009 (22) | 0,913 0,720 - 0,989 21/23 11/11 Biais 2009 (23) | 1,000 0,832 - 1,000 20/20 8/10 Preau 2010 (24) | 0,857 0,572 - 0,982 12/14 18/20 ------Pooled Sen | 0,894 0,841 - 0,934 ------Heterogeneity chi-squared = 13,07 (d.f.= 7) p = 0,070 Inconsistency (I-square) = 46,4 % No. studies = 8. Filter OFF Add 1/2 to all cells of the studies with zero

Summary Specificity

Study | Spe [95% Conf. Iterval.] TP/(TP+FN) TN/(TN+FP) ------Lafanechere 2006(18) | 0,833 0,516 - 0,979 9/10 10/12 Monnet 2006 (19) | 0,941 0,803 - 0,993 36/37 32/34 Lamia 2007 (20) | 1,000 0,715 - 1,000 10/13 11/11 Maizel 2007 (21) | 0,824 0,566 - 0,962 16/17 14/17 Thiel 2009 (13) | 0,936 0,825 - 0,987 45/55 44/47 Monnet 2009 (22) | 1,000 0,715 - 1,000 21/23 11/11 Biais 2009 (23) | 0,800 0,444 - 0,975 20/20 8/10 Preau 2010 (24) | 0,900 0,683 - 0,988 12/14 18/20 ------Pooled Spe | 0,914 0,859 - 0,952 ------Heterogeneity chi-squared = 8,12 (d.f.= 7) p = 0,322 Inconsistency (I-square) = 13,8 % No. studies = 8. Filter OFF Add 1/2 to all cells of the studies with zero Summary Positive Likelihood Ratio (Random effects model)

Study | LR+ [95% Conf. Iterval.] % Weight ------Lafanechere 2006(18) | 5,400 1,499 - 19,459 13,25 Monnet 2006 (19) | 16,541 4,307 - 63,524 12,03 Lamia 2007 (20) | 18,000 1,174 - 276,06 2,92 Maizel 2007 (21) | 5,333 1,897 - 14,995 20,38 Thiel 2009 (13) | 12,818 4,259 - 38,583 17,93 Monnet 2009 (22) | 21,500 1,421 - 325,36 2,95 Biais 2009 (23) | 4,295 1,442 - 12,797 18,27 Preau 2010 (24) | 8,571 2,262 - 32,476 12,27 ------(REM) pooled LR+ | 7,880 4,942 - 12,566 ------Heterogeneity chi-squared = 5,47 (d.f.= 7) p = 0,603 Inconsistency (I-square) = 0,0 % Estimate of between-study variance (Tau-squared) = 0,0000 No. studies = 8. Filter OFF Add 1/2 to all cells of the studies with zero

Summary Negative Likelihood Ratio (Random effects model)

Study | LR- [95% Conf. Iterval.] % Weight ------Lafanechere 2006(18) | 0,120 0,018 - 0,784 5,86 Monnet 2006 (19) | 0,029 0,004 - 0,199 5,54 Lamia 2007 (20) | 0,261 0,104 - 0,651 19,63 Maizel 2007 (21) | 0,071 0,011 - 0,484 5,65 Thiel 2009 (13) | 0,194 0,110 - 0,342 35,90 Monnet 2009 (22) | 0,109 0,033 - 0,353 13,22 Biais 2009 (23) | 0,031 0,002 - 0,486 2,83 Preau 2010 (24) | 0,159 0,044 - 0,577 11,37 ------(REM) pooled LR- | 0,146 0,091 - 0,235 ------Heterogeneity chi-squared = 8,44 (d.f.= 7) p = 0,295 Inconsistency (I-square) = 17,1 % Estimate of between-study variance (Tau-squared) = 0,0793 No. studies = 8. Filter OFF Add 1/2 to all cells of the studies with zero Summary Diagnostic Odds Ratio (Random effects model)

Study | DOR [95% Conf. Iterval.] % Weight ------Lafanechere 2006(18) | 45,000 3,465 - 584,34 9,63 Monnet 2006 (19) | 576,00 49,843 - 6656,5 10,57 Lamia 2007 (20) | 69,000 3,174 - 1499,9 6,68 Maizel 2007 (21) | 74,667 6,951 - 802,04 11,24 Thiel 2009 (13) | 66,000 17,016 - 255,99 34,47 Monnet 2009 (22) | 197,80 8,737 - 4477,9 6,51 Biais 2009(23) | 139,40 6,034 - 3220,3 6,42 Preau 2010 (24) | 54,000 6,668 - 437,31 14,48 ------(REM) pooled DOR | 89,040 40,176 - 197,33 ------Heterogeneity chi-squared = 3,30 (d.f.= 7) p = 0,856 Inconsistency (I-square) = 0,0 % Estimate of between-study variance (Tau-squared) = 0,0000 No. studies = 8. Filter OFF Add 1/2 to all cells of the studies with zero

Analysis of Diagnostic Threshold

------Spearman correlation coefficient: 0,611 p-value= 0,108 (Logit(TPR) vs Logit(FPR)

------Moses' model (D = a + bS) Weighted regression (Inverse Variance) Var Coeff. Std. Error T p-value ------a 4,536 0,413 10,983 0,0000 b( 1) 0,207 0,335 0,618 0,5595

------Tau-squared estimate = 0,0000 (Convergence is achieved after 1 iterations) Restricted Maximum Likelihood estimation (REML)

No. studies = 8 Filter OFF Add 1/2 to all cells of the studies with zero Pooling analysis of sensitivity, specificity, likelihood ratio and diagnostic odds ratio for PLR- induced changes in pulse pressure (PLR-cPP).

Summary Sensitivity

Study | Sen [95% Conf. Iterval.] TP/(TP+FN) TN/(TN+FP) ------Monnet 2006 (19) | 0,595 0,421 - 0,752 22/37 29/34 Monnet 2009 (22) | 0,478 0,268 - 0,694 11/23 10/11 Preau 2010 (24) | 0,786 0,492 - 0,953 11/14 17/20 ------Pooled Sen | 0,595 0,474 - 0,707 ------Heterogeneity chi-squared = 3,57 (d.f.= 2) p = 0,168 Inconsistency (I-square) = 44,0 % No. studies = 3. Filter OFF Add 1/2 to all cells of the studies with zero

Summary Specificity

Study | Spe [95% Conf. Iterval.] TP/(TP+FN) TN/(TN+FP) ------Monnet 2006 (19) | 0,853 0,689 - 0,950 22/37 29/34 Monnet 2009 (22) | 0,909 0,587 - 0,998 11/23 10/11 Preau 2010 (24) | 0,850 0,621 - 0,968 11/14 17/20 ------Pooled Spe | 0,862 0,753 - 0,935 ------Heterogeneity chi-squared = 0,28 (d.f.= 2) p = 0,871 Inconsistency (I-square) = 0,0 % No. studies = 3. Filter OFF Add 1/2 to all cells of the studies with zero

Summary Positive Likelihood Ratio (Random effects model)

Study | LR+ [95% Conf. Iterval.] % Weight ------Monnet 2006 (19) | 4,043 1,724 - 9,480 54,89 Monnet 2009 (22) | 5,261 0,774 - 35,773 10,85 Preau 2010 (24) | 5,238 1,781 - 15,402 34,26 ------(REM) pooled LR+ | 4,546 2,418 - 8,547 ------Heterogeneity chi-squared = 0,16 (d.f.= 2) p = 0,923 Inconsistency (I-square) = 0,0 % Estimate of between-study variance (Tau-squared) = 0,0000 No. studies = 3. Filter OFF Add 1/2 to all cells of the studies with zero Summary Negative Likelihood Ratio (Random effects model)

Study | LR- [95% Conf. Iterval.] % Weight ------Monnet 2006 (19) | 0,475 0,314 - 0,719 46,00 Monnet 2009 (22) | 0,574 0,372 - 0,885 43,32 Preau 2010 (24) | 0,252 0,091 - 0,699 10,69 ------(REM) pooled LR- | 0,482 0,340 - 0,682 ------Heterogeneity chi-squared = 2,63 (d.f.= 2) p = 0,269 Inconsistency (I-square) = 23,9 % Estimate of between-study variance (Tau-squared) = 0,0237 No. studies = 3. Filter OFF Add 1/2 to all cells of the studies with zero

Summary Diagnostic Odds Ratio (Random effects model)

Study | DOR [95% Conf. Iterval.] % Weight ------Monnet 2006 (19) | 8,507 2,683 - 26,971 58,94 Monnet 2009 (22) | 9,167 1,003 - 83,767 16,03 Preau 2010 (24) | 20,778 3,536 - 122,10 25,02 ------(REM) pooled DOR | 10,765 4,439 - 26,107 ------Heterogeneity chi-squared = 0,71 (d.f.= 2) p = 0,701 Inconsistency (I-square) = 0,0 % Estimate of between-study variance (Tau-squared) = 0,0000 No. studies = 3. Filter OFF Add 1/2 to all cells of the studies with zero