Apersistent dilemma for nutrition support practitioners

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1 Originl Communiction Anlysis of Estimtion Methods for Resting Metbolic Rte in Criticlly Ill Adults Dvid C. Frnkenfield, MS, RD, CNSD 1 ; Abigil Colemn, MS, RD, CNSD 1 ; Shoib Alm, MD 2 ; nd Robert N. Cooney, MD 3 Finncil disclosure: none declred. Journl of Prenterl nd Enterl Nutrition Volume 33 Number 1 Jnury/Februry Americn Society for Prenterl nd Enterl Nutrition / hosted t Bckground: Prediction of metbolic rte is n importnt prt of the nutrition ssessment of criticlly ill ptients, yet there re limited dt regrding the best eqution to use to mke this prediction. Methods: Stndrdized indirect clorimetry mesurements were mde in 202 ventilted, dult criticl cre ptients, nd resting metbolic rte ws clculted using the following equtions: Penn Stte eqution, Fisy, Brndi, Swinmer, Ireton-Jones, Mifflin, Mifflin 1.25, Hrris Benedict, Hrris Benedict 1.25, Hrris Benedict using djusted weight for obesity, nd ech of the djusted weight versions of Hrris Benedict The subjects were subgrouped by ge nd obesity sttus (young nonobese, young obese, elderly nonobese, elderly obese). Performnce of ech eqution ws ssessed using bis, precision, nd ccurcy rte sttistics. Results: Accurcy rtes in the study popultion rnged from 67% for the Penn Stte eqution to 18% for the weight-djusted Hrris Benedict eqution (without multipliction). Within subgroups, the highest ccurcy rte ws 77% in the elderly nonobese using the Penn Stte eqution nd the lowest ws 0% for the weight-djusted Hrris Benedict eqution. The Penn Stte eqution ws the only eqution tht ws unbised nd precise cross ll subgroups. The obese elderly group ws the most difficult to predict. Therefore, seprte regression ws computed for this group: Mifflin(0.71) + Tmx(85) + Ve(64) Conclusions: The Penn Stte eqution provides the most ccurte ssessment of metbolic rte in criticlly ill ptients if indirect clorimetry is unvilble. An lternte form of this eqution for elderly obese ptients is presented, but hs yet to be vlidted. (JPEN J Prenter Enterl Nutr. 2009;33:27-36) Keywords: cre resting metbolic rte; indirect clorimetry; criticl Apersistent dilemm for nutrition support prctitioners in criticl cre is the ccurte ssessment of metbolic rte. Although mesurement of metbolic rte using indirect clorimtery provides the most ccurte ssessment, most clinicins do not hve ccess to the equipment. Consequently, stndrdized equtions re commonly used to estimte the metbolic rte for this ptient popultion. Further complicting mtters, there re numerous equtions vilble for estimtion, but very little informtion compring the equtions to one nother or vlidting them ginst mesured metbolic rte. The Americn Dietetic Assocition recently undertook n evidence-bsed evlution of the vlidity of vrious equtions, nd could find only limited evidence tht ny of them were vlid. 1 From the Deprtments of 1 Clinicl Nutrition, 2 Pulmonry Medicine, nd 3 Surgery, The Pennsylvni Stte University, College of Medicine, Hershey. Received for publiction Mrch 20, 2008; ccepted for publiction April 11, Address correspondence to: Dvid Frnkenfield, MS, RD, CNSD, Deprtment of Clinicl Nutrition Division of Nursing, Milton S. Hershey Medicl Center, Pennsylvni University, Hershey, PA 17033; e-mil: dfrnkenfield@psu.edu. The purpose of the current study ws to compre severl equtions for predicting resting metbolic rte in lrge smple of criticlly ill dults to determine which, if ny, hve clinicl usefulness. Within this smple of criticlly ill dults, we endevored to cpture brod rnge of body sizes nd ges. Methods The reserch project ws reviewed by the Institutionl Review Bord t the Penn Stte M.S. Hershey Medicl Center, which wived the requirement for informed consent becuse the study ws essentilly one of qulity improvement, using n FDA-pproved medicl device tht ws lredy in clinicl usge in our criticl cre units. Ptients were eligible if they were dmitted to n dult intensive cre unit (ICU), were t lest 18 yers old, required mechnicl ventiltion, nd hd orders written nd implemented for enterl or prenterl nutrition support. Ptients were excluded if n ir lek existed in their ventiltion circuit, if their FiO 2 ws > 60%, if they were undergoing intermittent hemodilysis (continuous renl replcement therpy ws llowed), if they were shivering or gitted, or if they hd limited support orders written. We excluded ptients with 27

2 28 Journl of Prenterl nd Enterl Nutrition / Vol. 33, No. 1, Jnury/Februry 2009 prplegi nd qudriplegi (becuse these cn ttenute metbolic rte compred with other criticlly ill ptients), nd cystic fibrosis (becuse of the potentil for excessive work t brething). As we re not burn center, no burn injuries were included. Most mesurements were undertken erly in the morning (between 05:00 nd 07:00), becuse the rooms were more likely to be quiet nd the ptients undisturbed t those times. A SensorMedics Delttrc MB-101 (Andrews, CA) monitor ws used for ll mesurements of resting metbolic rte. Gs clibrtion ws conducted before ech use, fter mnufcturer-recommended 30-minute wrmup period. Our mesurement protocol ws to conduct 30-minute test, discrding the first 5 minutes of mesurement nd requiring 10% coefficient of vrition for oxygen consumption nd crbon dioxide production on the remining 25 minutes of mesured dt. 2 If the mesurement ws interrupted by cre needs (most commonly to tke n X-ry or to perform neurologic exmintion), shorter mesurement period ws cceptble (minimum 5 minutes of dt with 5% coefficient of vrition). 2 Height typiclly ws obtined from fmily member nd confirmed by the reserchers. Weight ws generlly mesured, however, the weight used for clcultion ws either the dmission weight if it ws lower thn current weight (resoning tht the difference ws due to fluid ccumultion) or current weight if it ws lower thn dmission weight (resoning tht either weight loss hd occurred in ptients mesured lte in their sty or tht dmission weight ws elevted by resuscittion fluid). Clinicl dt were collected t the time of the clorimetry mesurement. These dt included informtion necessry to complete the vrious metbolic rte equtions (body weight, height, ge, gender, body temperture, minute ventiltion, tidl volume, respirtory rte, nd hert rte), nd to describe the condition of the ptient (medictions, blood pressure, lbortory dt, feeding rtes, nd composition of feeding). Sepsis-relted orgn filure ssessment (SOFA) scores were computed from these dt, 3 s n lterntive to Acute Physiology nd Chronic Helth Evlution (APACHE) or other physiologic scores becuse unlike APACHE, SOFA scores use dt obtined on the dy of the mesurement, do not hve n ge or premorbid condition component, nd llow the use of Glsgow Com Scle scores ltered by intubtion nd sedtion nd recorded on the dy of ssessment rther thn the dy of dmission. Eight equtions were vlidted simultneously (Tble 1). These included the Hrris Benedict eqution 4 (HBE; long with severl vrints of using 2 djustments [HBE(25) nd HBE(50)] to body weight for obese ptients 5,6 nd multiplying the bse equtions by 1.25), the Mifflin St. Jeor eqution 7 (long with vrint in which the Mifflin eqution ws multiplied by 1.25 stress fctor), the Americn College of Chest Physicins (ACCP) recommendtion (25 kcl/kg body weight, with vrint of using djusted body weight in obese ptients), 8 the Swinmer eqution, 9 the Ireton-Jones eqution, 10 the Penn Stte equtions (PSU; 3 vrints), 11,12 the Brndi eqution, 13 nd the Fisy eqution. 14 The result of ech of these equtions ws compred with the mesured vlue of resting metbolic rte for bis, precision, nd ccurcy rte. Bis ws ssessed by exmining the 95% confidence intervl of the difference between estimted nd mesured metbolic rte. 15 This method cptures the tendency of the eqution to underestimte or overestimte the true vlue. If the confidence intervl included zero, the eqution ws considered to be n unbised estimtor of resting metbolic rte. Precision ws ssessed by exmining the bsolute difference between estimted nd mesured resting metbolic rte, s percentge of resting metbolic rte (lso referred to s the root men squred prediction error). Becuse it uses bsolute difference, the cnceling effect of underestimtes nd overestimtes on the men is eliminted. An estimte ws considered precise if the root men squred prediction error ws 15% of mesurement. Accurcy ws ssessed by the percentge of estimtes tht fell within 10% of the mesurement (bove or below) nd by the incidence of lrge errors (lrge errors were considered nything > 15% bove or below the mesured rte). Accurcy rtes were compred sttisticlly with proportion nlysis (Minitb Relese 14, Stte College, PA). To minimize the risks of finding significnt reltions by chnce, inherent in multiple comprisons, we did not nlyze ll possible pirs but insted took the most ccurte eqution in ech subject group nd compred ll other equtions with it. The sme ws done for the incidence of lrge errors. P vlue ws set t.05. The subject smple ws initilly nlyzed s whole, nd then subgrouped by ge nd body size. The intention ws then to collpse the groups without regrd to ge if ge did not seem to ffect ccurcy. The subgroups were defined s follows: Young nonobese (ge <60 yers nd body mss index (BMI) < 30 kg/m 2 ), young obese (ge < 60 yers nd BMI 30 kg/m 2 ), elderly nonobese (ge 60 yers nd BMI < 30 kg/m 2 ), nd elderly obese (ge 60 yers nd BMI 30 kg/m 2 ). Results Between September 2006 nd December 2007, 202 criticlly ill ptients hd their resting metbolic rte mesured by indirect clorimetry using stndrd protocol. 2 Eightynine percent of these subjects hd n rteril blood gs nlysis performed within 24 hours of the indirect clorimetry mesurement. Thirty-two percent of ptients hd PO 2 /FiO 2 rtio consistent with Acute Lung Injury (men 246 ± 28) nd 36% hd PO 2 /FiO 2 rtio consistent with Acute Respirtory Distress Syndrome (ARDS; men 162 ± 30). 16 The subject group ws lrgely Cucsin (95%). The remining 10 subjects were of Africn, Asin,

3 Vlidtion of Metbolic Rte Equtions in Criticl Cre / Frnkenfield et l 29 Tble 1. Explntion of Equtions Used in the Study Hrris Benedict (bsic): Men: 13.75(wt) + 5(ht) 6.8(ge) + 66 Women: 9.6(wt) + 1.8(ht) 4.7(ge) Hrris Benedict (vrints): HBE(25) substitutes djusted body weight in obese ptients clculted s (Actul wt idel wt b ) idel wt HBE(25) 1.25 uses the HBE(25) vlue nd multiplies it by 1.25 stress fctor HBE(50) substitutes djusted body weight in obese ptients clculted s (djusted wt idel wt b ) idel wt HBE(50) 1.25 uses the HBE(50) vlue nd multiplies it by 1.25 stress fctor Mifflin St. Jeor: Men: 10(wt) (ht) 5(ge) + 5 Women: 10(wt) (ht) 5(ge) 161 Americn College of Chest Physicins (ACCP): 25kcl/kg (ctul wt in obese subjects) 25 kcl/kg (djusted wt in obese subjects) Swinmer: BSA(941) Age(6.3) + T(104) c + RR(24) c + Vt(804) c 4243 Ireton-Jones: Wt(5) Age(10) + Mle(281) + Trum(292) + Burn(851) Brndi: HBE(0.96) + HR(7) c + Ve(48) c 702 Penn Stte: PSU(HBE) = HBE(0.85) + Tmx(175) d + Ve(33) d 6344 PSU(HBE) = HBE(1.1) + Tmx(140) d + Ve(32) d 5340 PSU(m) = Mifflin(0.96) + Tmx(167) d + Ve(31) d 6212 Fisy: Wt(8) + Ht(14) + Ve(32) c + T(94) c 4834 Equtions re listed in chronologicl order except for the ACCP eqution to keep the ICU-specific equtions blocked together. This listing order is followed throughout this study. b Idel weight clculted from the Hmwi method 6 c The originl ppers do not specify whether these vlues re mximum vlues in the previous 24 hours or vlues obtined t the time of mesurement. We used vlues obtined t the time of mesurement. d Tmx is mximum body temperture in the previous 24 hours nd Ve is minute ventiltion t the time of mesurement, red from the ventiltor, not the clorimeter. BSA, body surfce re in meters squred; HBE, Hrris Benedict eqution; HBE, Hrris Benedict eqution djusted for weight; HR, hert rte in bets per minute; Ht, height; PSU, Penn Stte eqution; RR, respirtory rte in breths/min; T, body temperture in degrees centigrde; Tmx, mximum body temperture in pst 24 hrs, centigrde; Ve, expired minute ventiltion; Vt, tidl volume in L/breth; Wt, weight. or Hispnic ncestry. Fifty-five percent of the subjects were men nd 51% were ged t lest 60 yers. Forty-seven percent were obese, wheres only 1.5% were underweight (BMI < 19 kg/m 2 ). Twenty-six percent of subjects were dmitted fter blunt trumtic injury (lthough not excluded, there were no penetrting trum ptients in this group; ll injuries were due to motor vehicle crshes or flls), 32% were surgicl ptients, nd 42% were medicl ptients or ptients dmitted nd cred for by surgicl service but who hd not undergone surgery this dmission. Tble 2 shows other dt tht describe the level of cuity of the prticipnts in vrious wys besides physiology scores. Hypermetbolism ws defined s mesured resting metbolic rte t lest 15% bove tht predicted by the Mifflin St. Jeor eqution, bsed on n upper limit of error for this eqution in helthy people. 17 Using this definition, t lest 65% of the study popultion qulified s hypermetbolic. The incidence of hypermetbolism in the obese (60%) nd nonobese subjects (69%) ws not significntly different (P =.179). Men resting metbolic rte ws 2000 ± 533 kcl/d (rnge, kcl/d) nd men percentge of clculted Mifflin St. Jeor eqution vlue ws 123% ± 19% (rnge, 75% 214% of computed Mifflin vlue). Tble 3 shows the metbolic dt nd other ptient chrcteristics s broken down into the 4 subgroups. Bis sttistics re displyed in Tble 4. For the smple s whole, the PSU, Ireton-Jones, Mifflin 1.25, nd HBE(50) 1.25 equtions were unbised. A vried picture emerged when the subjects were subgrouped by ge nd BMI ctegory. The Mifflin equtions nd ll of the unmultiplied HBEs were consistently bised towrd underestimtion. The 1.25 multipliction fctor corrected this bis for the Mifflin eqution in ll subgroups. Multipliction of the HBE led to overestimtion in ll groups except the young nonobese subjects. Substituting 2 different djustments to body weight for obesity nd multiplying by 1.25 resulted in n unbised estimte of obese ptients for HBE(50) 1.25, but continued bis towrd underestimtion for HBE(25) The Swinmer eqution ws consistently bised towrd overestimtion in ll ptient ctegories, while

4 30 Journl of Prenterl nd Enterl Nutrition / Vol. 33, No. 1, Jnury/Februry 2009 Tble 2. Descriptive Dt for the Study Prticipnts (Continuous Mesures Expressed s Men With Stndrd Devitions nd Rnges) Vrible Quntity Hospitl dy of mesurement 8 ± 7 (2 64) ICU dy of mesurement 6 ± 4 (2 27) SOFA score on dy of mesurement 8 ± 3 (1 18) Receiving tube feeding lone 73% Receiving prenterl nutrition lone 20% Receiving combined feeding 3% Feeding held 4% Receiving inotropes 35% Receiving continuous sedtion 71% Receiving centrl venous pressure monitoring 65% Centrl venous pressure t time of mesurement (mm Hg) 12 ± 5 (1 31) Body temperture t time of mesurement ( C) 37.2 ± 0.8 ( ) Body temperture, mximum, previous 24 hours ( C) 37.9 ± 0.8 ( ) Minute ventiltion t time of mesurement (L/min) 10.1 ± 3.5 ( ) Minute ventiltion, mximum, previous 24 hours (L/min) 12.8 ± 4.4 (4.8 32) Hert rte t strt of study (bets/min) 90 ± 18 (51 126) Hert rte, mximum, previous 24 hours (bets/min) 107 ± 17 (66 153) PO 2 /FiO ± 97 (82 533) Men rteril pressure t time of mesurement (mm Hg) 83 ± 14 (54 133) Length of ICU sty (dys) 18 ± 15 (3 172) ICU mortlity rte 26% SOFA, sepsis-relted orgn filure score; ICU, intensive cre unit. Use of intermittent sedtion ws not recorded. the PSU(m) eqution ws consistently unbised cross ll ptient groups. The Fisy eqution ws bised towrd overestimtion in both of the elderly groups, but unbised in both of the young groups. The Brndi eqution ws bised towrd overestimtion in both of the obese groups, but unbised in both of the nonobese groups. Both versions of the ACCP eqution were bised in ll subgroups. The Ireton-Jones, Mifflin, HBE, HBE 1.25, HBE(25), nd HBE(50) equtions were imprecise on the whole nd mong most of the subgroups. Mifflin 1.25 ws precise overll, but not mong the obese groups. HBE(25) 1.25 nd HBE(50) 1.25 were precise in young obese but not elderly obese subjects. Using djusted body weight in the ACCP eqution for obese subjects improved precision over using ctul weight, but the threshold for precision ws nonetheless not chieved. All of the remining equtions were precise overll, but only the PSU(m) nd PSU(HBE) equtions were precise cross ll ptient subgroups. The elderly obese subgroup ws prticulrly prone to inccurte estimtion (Tble 5). The unmultiplied Mifflin nd Hrris Benedict equtions (no mtter which weight ws used in obese subjects) were the lest ccurte equtions (Tble 6). In every instnce, multipliction of these equtions by 1.25 improved their ccurcy to levels similr to the Ireton- Jones, Swinmer, nd Brndi equtions. Use of djusted body weights in the HBE with multipliction by 1.25 improved the ccurcy of the eqution in obese subjects to levels similr to the Fisy nd PSU equtions. Adjusted weight improved the ccurcy of the ACCP eqution in obese subjects but overll these equtions were less ccurte thn the PSU, Fisy, Brndi, or Swinmer equtions. The PSU equtions hd the highest ccurcy rtes overll. All 3 versions of the PSU eqution nd the Fisy eqution were eqully ccurte in the young nonobese nd young obese groups. The Fisy eqution ws inccurte in both of the elderly groups. The PSU(m) eqution ws ccurte in the elderly nonobese group but not the elderly obese group. In fct, the elderly obese group ws consistently the most difficult for ny eqution to ccurtely predict. The incidence of lrge errors is shown in Tble 7 nd mximl errors re shown in Tble 8. Occurrence of lrge errors ws lowest for the PSU eqution, consistently high for the unmodified Mifflin eqution nd HBE, nd ws intermedite for the multiplied Mifflin, HBE, Fisy, nd Brndi equtions. Adjusted weight in the ACCP equtions reduced the incidence of lrge errors in obese ptients compred with the use of ctul body weight. Agin, the elderly obese group ws the most difficult group to predict. Becuse of the difficulty in predicting resting metbolic rte in the elderly obese group, these subjects were used to compute new regression eqution specific to them:

5 Vlidtion of Metbolic Rte Equtions in Criticl Cre / Frnkenfield et l 31 Tble 3. Ptient Chrcteristics, Mesured Resting Metbolic Rte, nd Predicted Resting Metbolic Rte Among the Subgroups (Men ± Stndrd Devition (Rnge)) Nonobese Obese Nonobese Obese Young Young Elderly Elderly Vrible (n = 52) (n = 47) (n = 52) (n = 51) Gender (% mle) Ht (cm) 173 ± 9 ( ) 176 ± 11 ( ) 168 ± 10 ( ) 167 ± 10 ( ) Wt (kg) 75 ± 13 (47 104) 124 ± 43 (80 334) 71 ± 12 (42 92) 102 ± 19 (71 164) BMI (kg/m 2 ) 25 ± 3 ( ) 40 ± 13 (30 112) 25 ± 3 ( ) 36 ± 6 ( ) Age (yers) 39 ± 13 (18 59) 44 ± 12 (18 59) 75 ± 9 (60 95) 70 ± 8 (60 87) SOFA 6 ± 3 (2 13) 8 ± 3 (4 18) 9 ±4 (2 17) 8 ± 3 (1 14) RMR 1991 ± 420 ( ) 2485 ± 524 ( ) 1630 ± 313 ( ) 1941 ± 498 ( ) HBE 1646 ± 235 ( ) 2256 ± 662 ( ) 1358 ± 196 ( ) 1700 ± 296 ( ) HBE ± 294 ( ) 2820 ± 828 ( ) 1698 ± 244 ( ) 2125 ± 370 ( ) HBE(25) 1646 ± 235 ( ) 1795 ± 362 ( ) 1358 ± 196 ( ) 1389 ± 233 ( ) HBE(25) ± 294 ( ) 2244 ± 453 ( ) 1698 ± 244 ( ) 1734 ± 292 ( ) HBE(50) 1646 ± 236 ( ) 1921 ± 428 ( ) 1358 ± 195 ( ) 1490 ± 245 ( ) HBE(50) ± 294 ( ) 2401 ± 535 ( ) 1698 ± 244 ( ) 1863 ± 306 ( ) Mifflin 1581 ± 218 ( ) 2063 ± 504 ( ) 1313 ± 233 ( ) 1614 ± 282 ( ) Mifflin ± 272 ( ) 2578 ± 630 ( ) 1641 ± 291 ( ) 2017 ± 353 ( ) ACCP (wt) 1871 ± 313 ( ) 3098 ± 1063 ( ) 1768 ± 290 ( ) 2544 ± 463 ( ) ACCP(MAW) 1871 ± 313 ( ) 2150 ± 445 ( ) 1768 ± 290 ( ) 1799 ± 296 ( ) Swinmer 2051 ± 342 ( ) 2596 ± 401 ( ) 1709 ± 320 ( ) 2138 ± 363 ( ) Ireton-Jones 2252 ± 271 ( ) 2345 ± 338 ( ) 1712 ± 220 ( ) 1870 ± 253 ( ) PSU(HBE) 1924 ± 324 ( ) 2507 ± 579 ( ) 1617 ± 281 ( ) 1982 ± 379 ( ) PSU(HBE) 2090 ± 360 ( ) 2319 ± 478 ( ) 1718 ± 309 ( ) 1821 ± 378 ( ) PSU(m) 1934 ± 317 ( ) 2463 ± 492 ( ) 1624 ± 324 ( ) 1980 ± 383 ( ) Brndi 1998 ± 365 ( ) 2613 ± 685 ( ) 1676 ± 342 ( ) 2054 ± 464 ( ) Fisy 2001 ± 322 ( ) 2488 ± 429 ( ) 1841 ± 307 ( ) 2151 ± 339 ( ) ACCP, Americn College of Chest Physicins; BMI, body mss index; HBE, Hrris Benedict eqution; HBE, Hrris Benedict eqution djusted for weight; MAW, metboliclly ctive weight, in kg; PSU, Penn Stte eqution; SOFA, sepsis-relted orgn filure ssessment. Tble 4. Bis of the Vrious Equtions (95% Coefficient of Vrition for the Difference Between Clculted nd Mesured Resting Metbolic Rte) Nonobese Obese Nonobese Obese Eqution All Young Young Elderly Elderly HBE 323 to to to to to 126 HBE to to 151 b 162 to to to 302 HBE(25) 507 to to to to to 444 HBE to to 151 b 322 to to to 100 HBE(50) 449 to to to to to 341 HBE(50) to 39 b 17 to 151 b 183 to 15 b 12 to to 30 b Mifflin 423 to to to to to 215 Mifflin to 88 b 96 to 67 b 38 to 225 b 47 to 69 b 37 to 189 b ACCP (wt) 213 to to to to to 749 ACCP (MAW) 162 to to to to to 28 Swinmer 75 to to to to to 280 Ireton-Jones 13 to 89 b 157 to to to to 31 b PSU(HBE) 38 to 38 b 125 to 6 60 to 144 b 61 to 35 b 51 to 133 b PSU(HBE) 53 to 21 b 40 to to to to 32 PSU(m) 43 to 29 b 118 to 6 b 92 to 85 b 57 to 43 b 49 to 127 b Brndi 29 to to 69 b 3 to to 103 b 15 to 210 Fisy 72 to to 74 b 85 to 92 b 160 to to 298 The confidence intervl must include zero to be considered unbised. Bised estimtes with negtive vlues indicte underestimtion nd those with positive vlues represent overestimtion. b Unbised. See Tble 3 for n explntion of bbrevitions.

6 32 Journl of Prenterl nd Enterl Nutrition / Vol. 33, No. 1, Jnury/Februry 2009 Tble 5. Precision of the Vrious Equtions (Root Squre Men Prediction Error) Young Young Elderly Elderly Eqution All Nonobese Obese Nonobese Obese HBE HBE b HBE(25) HBE(25) b b 8 14 b HBE(50) HBE(50) b b 8 14 b Mifflin Mifflin b 8 14 b b ACCP (wt) b ACCP (MAW) b 9 15 b Swinmer b 7 11 b 9 14 b 8 13 b Ireton-Jones b 7 13 b b PSU(HBE) 9 11 b 8 11 b 7 12 b 6 11 b PSU(HBE) 9 11 b 8 12 b 7 11 b 7 12 b 9 14 b PSU(m) 8 11 b 7 11 b 7 11 b 6 11 b 9 15 b Brndi b 6 11 b 8 14 b 8 12 b Fisy b 7 11 b 7 11 b Must be within 15% to be considered precise. b Precise. See Tble 3 for n explntion of bbrevitions. Tble 6. Accurcy Rtes of the Equtions (Percentge of Estimtes 10% Different From Mesured) Young Young Elderly Elderly Eqution All Nonobese Obese Nonobese Obese HBE 34 b 31 b 45 b 27 b 35 b HBE b 50 b 45 b 56 b 33 b HBE(25) 18 b 31 b 0 b 27 b 12 b HBE(25) b 50 b b 33 b HBE(50) 22 b 31 b 9 27 b 22 b HBE(50) b 50 b b 43 Mifflin 25 b 23 b 21 b 21 b 35 b Mifflin b b 54 b 43 ACCP (wt) 35 b 44 b 34 b 50 b 12 b ACCP (MAW) 46 b 44 b 47 b 50 b 43 Swinmer 54 b Ireton-Jones 46 b 33 b 49 b 50 b 51 PSU(HBE) PSU(HBE) PSU(m) Brndi 55 b Fisy 53 b b 39 b Best eqution in subgroup. All sttisticl comprisons re to this eqution. b P <.05 compred with best eqution in the subgroup. See Tble 3 for n explntion of bbrevitions. Tble 7. Incidence of Lrge Errors (Percentge of Estimtes >15% Different From Mesured) Young Young Elderly Elderly Eqution All Nonobese Obese Nonobese Obese HBE 51 b 54 b 45 b 60 b 47 HBE b 33 b 38 b b HBE(25) 70 b 54 b 60 b 60 b 80 b HBE(25) b 33 b 21 31b 37 HBE(50) 65 b 54 b 81 b 60 b 69 b HBE(50) b 33 b b 37 Mifflin 60 b 67 b 60 b 67 b 45 Mifflin b b ACCP (wt) 51 b 37 b 53 b 37 b 78 b ACCP (MAW) 43 b 37 b 40 b 37 b 47 Swinmer 30 b b Ireton-Jones 39 b 58 b 34 b PSU(HBE) PSU(HBE) b PSU(m) Brndi 33 b b Fisy 36 b b 49 Best eqution in subgroup. All sttisticl comprisons re to this eqution. b P <.05 compred with best eqution in the subgroup. See Tble 3 for n explntion of bbrevitions.

7 Vlidtion of Metbolic Rte Equtions in Criticl Cre / Frnkenfield et l 33 Tble 8. Mximum Errors for Ech Eqution (Percent Difference From Mesured Vlue) Young Nonobese Young Obese Elderly Nonobese Elderly Obese Eqution Min Mx Min Mx Min Mx Min Mx HBE HBE HBE(25) HBE(25) HBE(50) HBE(50) Mifflin Mifflin ACCP (wt) ACCP (MAW) Swinmer Ireton-Jones PSU(HBE) PSU(HBE) PSU(m) Brndi Fisy See Tble 3 for n explntion of bbrevitions. Resting metbolic rte = Mifflin(0.71) + Tmx(85) + Ve(64) 3085 (N = 51, R 2 = 0.66, F 47,3 = 30.1). Hving identified the PSU(m) eqution s the one hving the highest ccurcy rte, we then undertook secondry nlysis to determine whether severity of illness hd n effect on the performnce of the eqution. We nlyzed the ptients by SOFA score (1-5, 6-10, or >10) nd found no difference in ccurcy rte (68%, 64%, nd 69%). Accurcy rte in febrile ptients nd febrile ptients ws identicl (67%). The eqution ws ccurte in 77% of trum ptients, 66% of surgicl ptients, nd 62% of medicl ptients (P <.64 medicl vs trum) but of note there were more obese elderly ptients in the medicl group (28%) thn the trum group (13%), which my ccount for the downwrd trend in ccurcy between medicine nd trum. Discussion The results of the current study represent the lrgest published series compring currently vilble metbolic rte equtions in diverse popultion of dult criticl cre ptients to dte. The study popultion is 4 times lrger thn our initil report 12 nd evlutes 6 dditionl equtions. The rnge of body size nd ge cptured in this rticle llows more complete ssessment of how these equtions perform in young nd old, obese nd nonobese dults (popultions tht re incresingly prevlent nd whose metbolic rte is difficult to predict using stndrd equtions). The study lso fills gp in current knowledge identified by the Americn Dietetic Assocition (ADA) evidence-nlysis work group on criticl illness, which ws unble to determine the clinicl utility of currently vilble predictive equtions due to limited dt. 1 The initil pln for hndling the dt ws to subgroup by ge nd obesity sttus, nd then collpse these divisions to just obesity sttus if ge did not ffect the performnce of the equtions. However, we were unble to collpse the groups becuse the initil nlysis showed tht the combintion of obesity nd ge did ffect the ccurcy rte. For exmple, the PSU(m) eqution predicted ccurtely in 77% of nonobese elderly ptients, but in only 53% of obese elderly ptients. Similr decreses occurred for most of the other equtions s well. It is worth noting tht the elderly groups hd lower percentges of men in them, nd this ws especilly true for the elderly obese group. In other studies predicting metbolic rte, ccurcy of prediction is lower in women thn in men, 4,17 so the prepondernce of women in the obese elderly group my in prt explin why this group ws difficult to predict in the current study. Becuse the combintion of incresed body mss index nd ge did ffect eqution performnce, we chose to compute new regression for these subjects. We re unble to verify whether this new eqution solves the performnce problem without first performing vlidtion study (now under wy). HBE Developed in 1919 nd still in use, the HBE is in form nd intent similr to the Mifflin eqution (weight, height,

8 34 Journl of Prenterl nd Enterl Nutrition / Vol. 33, No. 1, Jnury/Februry 2009 ge, nd gender s fctors intended to predict resting metbolic rte in helthy people). 4 We included it in this nlysis becuse it hs been used in criticl cre for long time nd probbly continues to be used despite n evidence nlysis recommending otherwise. 1 There re mny permuttions to the HBE in criticl cre. We chose to nlyze 6: the HBE lone, HBE multiplied by 1.25, HBE djusted for obesity by dding 25% of excess weight to the idel weight nd multiplying this quntity by 1.25, HBE djusted for obesity by dding 50% of excess weight to idel weight then multiplying this quntity by We found tht, overll, the HBEs performed less fvorbly thn the PSU equtions, but in certin subgroups the HBE(50) 1.25 version gve similr results to PSU(m). Overll, we confirm the ADA evidence nlysis workgroup recommendtion tht this eqution not be used in criticl cre. 1 Mifflin The Mifflin eqution ws developed in 1990 for helthy people, nd so it is not surprising tht in its unmodified form it did not work well in criticlly ill ptients. 5 We pplied it minly for descriptive purposes. The eqution ws found to be bised (underestimtion) nd imprecise. The eqution is inccurte, but it is notble even so tht, in 25% of ll subjects, the unmodified eqution ws ccurte (these ptients were probbly not hypermetbolic). Multipliction of the eqution by 1.25 ( firly common modifiction in clinicl cre) improved the bis, precision, nd ccurcy of this eqution. ACCP The ACCP published consensus sttement on nutrition in criticl cre in An energy ssessment of 25 kcl/kg usul body weight ws believed by the consensus pnel to be resonble stndrd for most ptients. This vlue ws not referenced, but does fll within the rnge of other firly widely pplied stndrds (20 35 kcl/kg). We tested this eqution s reported by the consensus group (25 kcl/kg usul weight for ll ptients, including the obese) nd lso modifying the body weight for obesity (metboliclly ctive weight clculted s 25% of the excess weight dded to the idel weight). Although use of metboliclly ctive weight incresed the ccurcy nd decresed the mgnitude of error of this eqution, significnt inccurcy remined with this eqution nd therefore we conclude tht energy ssessments bsed solely on body weight re not useful in criticl cre nutrition ssessment. Swinmer The Swinmer eqution dtes bck to It ws developed in Cnd on mixed criticl cre popultion of 112 subjects. In the current vlidtion study, the Swinmer eqution ws found to be bised (overestimtion) but precise (except in obese elderly subjects). However, the ccurcy rtes mong the subgroups were generlly lower thn for the PSU equtions, nd roughly on pr with the Fisy nd Brndi equtions nd the multiplied Mifflin eqution nd HBEs. A previous vlidtion study exists for the Swinmer eqution. This ws the study performed by McDonld nd Hildebrndt, 18 compring estimtes ginst mesurement tht ws probbly totl rther thn resting metbolic rte in ptients with BMI < 30 kg/m 2. In the study by McDonld nd Hildebrndt, the Swinmer eqution ws ccurte 55% of the time, compred with 61% in our nonobese subjects (combining both ge groups). Ireton-Jones (1992) The Ireton-Jones eqution is probbly the best-known nd most commonly used ICU-specific eqution for predicting resting metbolic rte. 10 It ws developed in the United Sttes (Texs) from 65 criticlly ill ptients, hlf of whom were burn victims. We found in the current study tht the Ireton-Jones eqution ws unbised overll but bised towrd overestimtion in nonobese ptients nd towrd underestimtion in obese ptients (ie, the overestimtes cnceled the underestimtes, leding to n pprent unbised estimte in the group s whole). The eqution just missed the threshold for precision, due to imprecise results in the young, nonobese subjects. The ccurcy rte is lower thn ny of the equtions tested in this study, with the exception of the unmodified Mifflin eqution nd HBEs. Severl vlidtion studies of the Ireton-Jones eqution exist. Both McDonld nd Hildebrndt 18 nd Flncbum et l 19 concluded tht the eqution ws not sufficiently ccurte, but our own erlier vlidtion study did not confirm this (overll ccurcy rte in tht study ws 60%). 12 However, in the current, lrger study, we do confirm tht the Ireton-Jones eqution is inccurte. PSU Equtions The PSU equtions were developed from mixed ICU popultion of 169 prticipnts in Pennsylvni. 11,12 The dt were collected between 1992 nd The equtions re in form similr to Fisy, Brndi, nd Swinmer in tht they use vribles relted to body size (the HBE or Mifflin St. Jeor eqution) nd inflmmtory response (body temperture nd minute ventiltion). In the vlidtion smple s whole, ll of the PSU equtions were unbised nd precise. However, in the subgroup nlysis, only the PSU(m) version ws unbised nd precise throughout. Accurcy rtes mong the subgroups were highest for PSU(m) except for

9 Vlidtion of Metbolic Rte Equtions in Criticl Cre / Frnkenfield et l 35 the elderly obese group, which ws not predicted well by ny eqution. The lternte eqution for this group needs to be vlidted before it is used. One concern we hd ws tht the eqution might perform differently t different levels of illness severity. Although this ws post hoc ddition to the reserch pln, it is nonetheless n importnt point tht bsed on the prmeters used to group the ptients physiologiclly (SOFA score, presence of fever, nd reson for dmission), the PSU(m) eqution ccurcy did not diminish with cuity. Brndi The Brndi eqution ws developed in Itly in 1999 from 26 dult trum criticl cre ptients. 13 The uthors noted tht injury severity score did not predict resting metbolic rte in their subjects, nd the eqution s result contins only body size nd inflmmtory response vribles. In our study, the Brndi eqution ws unbised nd precise in both nonobese groups, nd ccurcy rte followed suit, but filed to predict ccurtely in the obese groups. The eqution did predict resting metbolic rte better in trum ptients (67%) thn in nontrum ptients (51%), but this is not better thn the ccurcy rte of the PSU(m) in trum (76%). Furthermore, it must lso be noted tht the incidence of obesity ws lower in our trum ptients (33%) thn our nontrum ptients (54%), which could explin why ccurcy rtes re higher in the trum ptients. To our knowledge, the current study represents the first published vlidtion study of the Brndi eqution. Fisy The Fisy eqution ws developed in 2003 from 70 dult criticl cre ptients (pprently medicl ptients) in Frnce. 14 The men ge of the prticipnts ws 61 yers, so it is somewht surprising tht the older groups in the current study were much more difficult to ccurtely estimte thn the younger groups. Within our ge groups, obesity did not seem to hve detrimentl effect on the ccurcy of this eqution. The Fisy eqution overll ws bised towrd overestimtion nd ws inccurte, but this ws lrgely result of its performnce in the older ptients. In younger people, the Fisy eqution ws unbised nd precise, with ccurcy rtes similr to those of the Penn Stte equtions. There re no other published vlidtion studies of the Fisy eqution to our knowledge. Limittions The differences in ccurcy rte mong the subgroups should be ssessed by the reder without hevy relince on the sttisticl comprisons becuse there my be power problems. As n exmple, the ccurcy rte between PSU(m) nd Fisy in the whole group (67% vs 53% with n n of 202) ws similr to the difference between Fisy nd Brndi in the young obese group (72% vs 55% with n n of 47) nd yet only the contrst in the lrger group ws sttisticlly significnt. An dditionl limittion is tht severl ptient popultions were not represented in the current study, including children, spinl cord injury with prplegi or qudriplegi, burn injury, nd penetrting trum. Conclusion This study is the lrgest nd most complete vlidtion study of metbolic rte equtions for criticl cre yet published. The PSU(m) eqution is the most consistent eqution cross the ptient subgroups nd cross the sttisticl mesures, lthough in some subgroups nd mesures, the other equtions worked similrly well. The exception for ll the equtions is the group of ptients over the ge of 60 yers with BMI > 30 kg/m 2, which ws difficult to predict no mtter which eqution is used. Bsed on these findings, we recommend the PSU(m) eqution for use in criticl cre nutrition ssessment. An lternte form of this eqution is proposed for elderly obese ptients, but it must first be vlidted. References 1. Frnkenfield D, Hise M, Mlone A, Russell M, Grdwell E, Compher C. Evidence Anlysis Working Group. 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