Severe hypoglycaemia in diabetic patients in Pre-hospital and Emergency Department care: A cross-sectional survey

Es e es e al. BMC Res No es (2018) 11:249 h ps://doi.o g/10.1186/s13104-018-3363-0 RESEARCH NOTE Se e e hypoglycaemia in diabe ic pa ien s in P e-hospi al and Eme gency Depa men ca e: a c oss-sec ional su ey Césa Es e es1,2,3*, Celes ino Ne es1,2,3, João Jaime Sá4 and Da ide Ca alho1,2,3 Abs ac Objec i e: We aimed o cha ac e ize hypoglycaemia episodes and pa ien s examined by a P e-hospi al Medical Eme gency Uni (PH) and in he Eme gency Depa men (ED) o ou hospi al. Resul s: We iden i ied 86 episodes o se e e hypoglycaemia (PH: n 37; ED: n 49; bo h: n 12). Hypoglycaemia accoun ed o 4.7% o all eme gency calls a ended by he PH (n 793) and 0.11% o all ED episodes (n 54,366). Among episodes examined by he PH, 64.5% o in ol ed pa ien s had ype 2 diabe es and 54.1% we e no e e ed o he ED. T anspo a ion o he pa ien o he ED was mo e likely in ype 2 diabe es (p = 0.014). Among episodes e alua ed in he ED 66.1% o he pa ien s we e mo e han 65 yea s old and 81.4% had ype 2 diabe es. 66% o he pa ien s we e insulin ea ed. One- hi d o examined pa ien s we e admi ed o he wa d, he majo i y ha ing ype 2 diabe es. Keywo ds: Hypoglycaemia, Eme gency ca e, Cos s, Diabe es melli us © The Au ho (s) 2018. This a icle is dis ibu ed unde he e ms o he C ea i e Commons A ibu ion 4.0 In e na ional License (h p://c ea i ecommons.o g/licenses/by/4.0/), which pe mi s un es ic ed use, dis ibu ion, and ep oduc ion in any medium, p o ided you gi e app op ia e c edi o he o iginal au ho (s) and he sou ce, p o ide a link o he C ea i e Commons license, and indica e i changes we e made. The C ea i e Commons Public Domain Dedica ion wai e (h p://c ea i ecommons.o g/ publicdomain/ze o/1.0/) applies o he da a made a ailable in his a icle, unless o he wise s a ed. In oduc ion Hypoglycaemia is a majo ba ie o he achie emen o op imal glycaemic con ol in diabe es (DM) [1, 2]. I is one o he mos common ad e se e ec s associa ed wi h an idiabe ic d ugs and is usually ecognized as being po en ially ha m ul o people wi h diabe es [3, 4]. The ACCORD [5], ADVANCE [6] and VADT [7] ials dem- ons a ed an inc ease in mo ali y in he case o in en- si ely- ea ed pa ien s wi h ype 2 diabe es (T2DM). In analysing he eason o his, one o he main hypo hesis is ha mo ali y was associa ed wi h hypoglycaemia isk. ADA [2] epo s on he subjec conside ha se e e hypoglycaemia is a condi ion which equi es ano he pe son o ac i ely adminis e ca bohyd a es, glucagon, o ake o he co ec i e ac ions. In ype 1 diabe es (T1DM), he incidence o se e e hypoglycaemia is 115 [8]–320 [9] episodes/pa ien -yea , and se e e hypoglycaemia may be he cause o dea h o 4–10% [10] o pa ien s. Fo indi iduals wi h T2DM, he isk o se e e hypoglycaemia is lowe . I mainly occu s in indi iduals ha ha e been ea ed wi h sec e agogues o insulin, in olde pa ien s wi h mul iple como bidi ies, ecen hospi aliza ion and polymedica ed pa ien s [2]. Hypoglycaemia in DM has been ecognized as a d i e o inc eased cos s o heal h- ca e sys ems. In Po ugal, da a ega ding hypoglycaemia is sca ce [11] as he e a e no s uc u ed da abases ega ding eme - gency episodes, and diabe es da abases a e based on appoin men eco ds which do no include in o ma ion abou hypoglycaemia [12]. Howe e , in 2015, an es i- ma ed 13.3% [12] o he popula ion had DM and may be a isk o ea men induced hypoglycaemia. The au ho s in end o e alua e he p e alence o hypoglycaemia and ea men p o ocols implemen ed in he Eme gency Depa men (ED) o a leading hospi al, and also in he associa ed P e-hospi al Medical Eme gency Uni (PH), as well as he c i e ia o admission o he wa d. We will also look in o he causes o e alua ed hypoglycaemia episodes. Open Access BMC Resea ch No es *Co espondence: cesa ma queses e [email p o ec ed] 1 Endoc inology, Diabe es and Me abolism Depa men , Cen o Hospi ala São João, Alameda P o . He nani Mon ei o, 4200-319 Po o, Po ugal Full lis o au ho in o ma ion is a ailable a he end o he a icle Page 2 o 5 Es e es e al. BMC Res No es (2018) 11:249 Main ex Me hods We pe o med a e ospec i e c oss-sec ional s udy o indi iduals wi h DM examined in he P e-hospi al and/ o ED se ing due o hypoglycaemia. Ou da a e e s o episodes ha ook place be ween he 1s o Janua y and he 31s o Ma ch, 2010, e alua ed by he PH o in he ED o ou hospi al, which p o ides ca e in a la ge ci y in Po ugal. We we en’ able o ex end he s udy pe iod due o so wa e limi a ions. In Po ugal, P e-hospi al Ca e is usually made by pa amedic pe sonnel. Some eams include medical doc o s ha can ea eme gen si u- a ions in an ou pa ien basis, wi h no need o anspo he pa ien o he hospi al. All eme gency episodes a e documen ed in he P e-hospi al Eme gency Uni ile and/ o in he elec onic heal h eco d so wa e used in he Eme gency Depa men –Ale ©. We sea ched he iles o he PH and he Ale © so wa e o da a on ED episodes, using he ICD-9 codes ha a e po en ially associa ed wi h DM and i s complica ions, o hypoglycaemia: 250 (diabe- es melli us), 251 (o he diso de s o panc ea ic in e nal sec e ion), 271 (diso de s o ca bohyd a e anspo and me abolism), 775.6 (hypoglycaemia) and 962 (poison- ing by ho mones and syn he ic subs i u es). We excluded pa ien s wi hou diabe es, as well as codi ica ion e o s. We eco ded he ollowing a iables: demog aphic da a, ype o diabe es, an idiabe ic d ugs, diabe es du a ion, ch onic diabe es complica ions, como bidi ies, p esence o neu ogenic o neu oglycopenic symp oms, Glasgow Coma Scale and glycaemia changes du ing he episode. We iden i ied he episodes ha esul ed in admission o he Sho S ay Uni (SSU), admission o he wa d and he como bidi ies ha could be ela ed wi h he decision o keep he pa ien in obse a ion. The SSU is a wa d whe e he pa ien can be kep o obse a ion o less han 24h, a e which i is conside ed o be an admission o he wa d. We used Mic oso O ice 2010 Excel and SPSS 20.0 o s a is ical analysis. When applicable, we used he χ2 and Mann–Whi ney es s. The esul s we e exp essed as mean ± s anda d de ia ion o median [qua iles]. We conside ed p < 0.05 as signi ican . Resul s We e iewed 793 eme gency calls e alua ed by he PH, o which 37 we e hypoglycaemia episodes (4.7%). We e iewed 54,366 ED episodes du ing he s udy pe iod o which 15,517 we e no associa ed wi h a de ini i e diag- nosis and he e o e we e excluded om he analysis. Among he emaining 38,849 episodes, we ound 102 episodes, o which 32 we e no associa ed wi h hypogly- caemia, 8 episodes occu ed in pa ien s wi hou diabe es and 1 episode ook place in he ED. Fo y- wo episodes we e diagnosed as “o he speci ied hypoglycaemia” and 19 as “hypoglycaemia, unspeci ied”— o alizing 61 epi- sodes o hypoglycaemia (0.11% o he o al ED episodes; 0.16% among episodes wi h a de ini i e diagnosis). In o al, we iden i ied 86 episodes o se e e hypoglycaemia: 37 examined by he PH, o which 12 we e e e ed o he ED and 49 episodes we e examined in he ED ha had no been p e iously examined by he PH. The episodes occu ed wi h 84 pa ien s, as 2 indi iduals had ecu en hypoglycaemia. P e‑hospi al Medical Eme gency Uni Twen y episodes (54.1%) did no esul in e e al o he ED and 13 (35.1%) occu ed be ween 24.00 and 08.00. The cha ac e iza ion o he examined pa ien s is p e- sen ed in Table1. People wi h T1DM we e signi ican ly younge han pa ien s wi h T2DM [40yea s (35.0–42.5) s 75yea s (68.5–77.8); p = 0.000; Mann–Whi ney es ], howe e he e we e no signi ican di e ences in diabe es du a ion (p = 0.203). All indi iduals wi h T2DM ea ed wi h o al agen s only we e using sulphonylu eas. Mean glycemia a p esen a ion was 32 ± 14.9 mg/dL and only one- hi d o pa ien s e e ed neu ogenic symp- oms. The e was a p e ious a emp o ea hypoglycae- mia by a ela i e in six episodes (16.2%). Thi y- i e cases we e ea ed on si e by a heal h ca e p o essional using hype onic glucose. The e was no e e ence o use o glucagon. Episodes in ol ing pa ien s wi h T2DM we e mo e equen ly associa ed wi h e e al o he ED han hose in indi iduals wi h T1DM [14 (70.0%) s 3 (25.0%); p = 0.027; χ2 es ]. Re usal o he pa ien was he eason why 17.6% o pa ien s we e no e alua ed in he ED. Eme gency Depa men Table 1 desc ibes he de ailed in o ma ion o pa ien s wi h hypoglycemia examined in he ED. The e was a high p e alence o signi ican como bidi ies, such as ch onic kidney disease (n 21, 34.4%), hea disease (n 20, 32.8%), ce eb o ascula disease (n 18, 29.5%), neoplas ic disease (n 8, 13.5%) and demen ia (n 7, 11.9%). De ails on he use o o al agen s can be ound in Table2. Nine een pa ien s we e using sulphonylu eas, o which 8 we e using gliben- clamide, 5 we e using glimepi ide and 4 we e using gli- clazide (missing 2). De ails on hypoglycaemia episodes in he ED can be ound in Table3. A he ime o a i al o he ED, 30 (49.2%) pa ien s we e hypoglycaemic (mean glycemia 43 ± 16.4mg/dL, 1 below 20mg/dL). Among hese, 16 (26.2%) we e diagnosed in he ED. None o he pa ien s admi ed in he ED whils hypoglycaemic was p e i- ously e alua ed by ou PH. In 32 (52.4%) pa ien s, he mean maximal glycaemia du ing he ED s ay was highe han 250 mg/dL. The e was a s a is ically signi ican Page 3 o 5 Es e es e al. BMC Res No es (2018) 11:249 di e ence in Glasgow Coma Scale be ween pa ien s ha we e admi ed in he ED du ing nigh ime and day ime [8.5 (3.0–15.0) s 15.0 (13.5–15.0) espec i ely; p = 0.046; Mann–Whi ney es ]. Diges i e sys em associa ed disease was he mos com- mon concu en cause o hypoglycemia (n 17, 27.9%), ollowed by insulin adminis a ion e o (n 8, 13.1%), acu e kidney inju y (n 7, 11.5%), skipped meal (n 7, 11.5%) and u ina y ac in ec ion (n 6, 9.8%). O he p e- cipi an s accoun o 13 episodes (21.3%) and 11 (18.0%) had no iden i ied cause. Pa ien s’ s ay in he hospi al Among 19 pa ien s admi ed, 2 s ayed in he SSU o mo e han 24h and he emaining we e admi ed o he wa d. In 19 pa ien s, 18 had T2DM, o which 9 we e using o al agen s only—all wi h sulphonylu ea—6 we e only using insulin and 3 we e ea ed wi h combined he apy. O he pa ien s admi ed o he wa d, 11 p esen ed ea- sons o admission o he han hypoglycaemia: (1) com- muni y acqui ed pneumoniae (n 4), (2) wo sening kidney unc ion (n 5), (3) myoca dial in a c ion o decompen- sa ed hea ailu e (n 3), (4) s oke (n 1), (5) lowe limb gang ene (n 1) and (6) social easons (n 1). Hospi al s ay median du a ion was 9days (minimum 3–maximum 130), acco ding o he ype and se e i y o como bidi ies. 17 (89.4%) pa ien s we e discha ged home and 2 pa ien s died du ing hospi al s ay. Follow up a e discha ge om he ED/wa d Since he ime pe iod o da a analysis up o Sep em- be 2013, 15 (25.4%) pa ien s died. The median ime lag be ween se e e hypoglycaemia episode and dea h was 9mon hs (minimum 4–maximum 21). Pa ien s ha died du ing ollow-up had a mean age o 72.9 ± 11.69yea s Table 1 Cha ac e iza ion o pa ien s wi h hypoglycaemia examined by he PH (n 37) and in he ED (n 59) OA o al agen s, DM1 ype 1 diabe es melli us, DM2 ype 2 diabe es melli us, DM3 o he causes o diabe es melli us P e-hospi al Eme gency Uni Eme gency Depa men Age (yea s) Mean ± SD: 60.7 ± 18.36 Min–max: 27–84 > 65 yea s: 19 (51.3%) Mean ± SD: 68.0 ± 15.26 Min–max: 23–93 > 65 yea s: 39 (66.1%) Gende Men: 10 (27.0%) Women: 26 (72.3%) Missing: 1 Men: 28 (47.5%) Women: 31 (52.5%) Type o diabe es melli us DM1: 11 (35.5%) DM2: 20 (64.5%) Missing: 6 DM1: 5 (8.5%) DM2: 48 (81.4%) O he : 6 (10.2%) Diabe es du a ion (yea s) 19.1 ± 8.37 Min–max: 10–30 16.2 ± 10.25 Min–max: 0–37 His o y o diabe es complica ions – Yes: 35 (59.3%) No: 24 (40.7%) His o y o se e e hypoglycaemia Yes: 8 Missing: 29 Yes: 12 (20.3%) No: 47 (79.7%) An idiabe ic agen s Only OA: 5 (26.3%) Only insulin: 9 (47.4%) OA plus insulin: 5 (26.3%) Missing: 18 Only OA: 20 (33.9%) Only insulin: 30 (50.8%) OA plus Insulin: 9 (15.2%) Table 2 Use o o al agen s in people wi h diabe es admi - ed in he ED o hypoglycemia DPPI DPP-IV inhibi o , SU sulphonylu ea, TZD hiazolidinedione, AGI alpha- glucosidase inhibi o Subg oups D ug class combina ion n O al agen s only, wi hou SU +Me o min and DPPI 1 +TZD 1 Missing 1 Sub o al 3 O al agen s only, including SU Mono he apy 5 +Me o min 7 +DPPI 1 +DPPI and me o min 3 +Me o min and AGI 1 Sub o al 17 O al agen s plus insulin +Me o min 3 +Me o min and DPPI 2 +Me o min, DPPI and SU 1 +Me o mina and AGI 1 +Me o min, TZD and SU 1 Missing 1 Sub o al 9 To al 29 Page 4 o 5 Es e es e al. BMC Res No es (2018) 11:249 and se e e como bidi ies. Among hese, ascula disease (n 9) and ch onic kidney disease (n 7) we e pa icula ly p e alen . Discussion We ound a signi ican p e alence o se e e hypoglycae- mia among pa ien s e alua ed by a PH. A s udy published in 2006 [13] ound ha hypoglycaemia is he mos com- mon eason o eme gency calls ela ed o diabe es o an idiabe ic he apy, accoun ing o 51% o e alua ions. We con i med ha he equency o e e al o he ED among pa ien s wi h T2DM is signi ican ly highe han among indi iduals wi h T1DM, as p e iously desc ibed [11]. In p e ious li e a u e, he p e alence o se e e hypogly- caemia in he ED is 0.37–0.4% [14, 15]. We ound a lowe igu e, which migh be ela ed o he ac ha he p e i- ous s udies ook place se e al yea s ago, and ha he p e- sc ip ion pa e n o an idiabe ic d ugs di e ed om ha o 2010, as well as ecommended glucose a ge s. In Po - ugal, mos new insulins a e ully and mos o al agen s a e pa ially eimbu sed. In one s udy [13], 93% o pa ien s was using insulin and only 1 pa ien did no ha e documen ed hypogly- caemia in he p e-hospi al con ex . In ou se ies, 54.4% o pa ien s we e using insulin (56.3% among indi idu- als wi h T2DM) and 16 (26.2%) we e diagnosed in he ED. I may be ha , in ou a ea, pa ien s and hei ela- i es migh no ha e su icien he apeu ic educa ion o he p e en ion, iden i ica ion and adequa e managemen o hypoglycaemia episodes. I is necessa y o de e mine wha he di icul ies a e o p e-hospi al diagnosis/e alu- a ion o hypoglycaemia. Rega ding hypoglycaemia ea men modali y, IV glu- cose was he p e e ed ea men while o he au ho s [13] no ed a high p e alence o glucagon-use. The same au ho s ound ha mos pa ien s a i ed a he ED s ill su e ing om hypoglycaemia. In ou s udy, nea ly hal o he pa ien s we e admi ed in ha condi ion. This may be ela ed o: (1) inadequa e p e-hospi al diagnosis; (2) e e al o pa ien s o he ED by ela i es due o symp- oms associa ed wi h undiagnosed hypoglycaemia; (3) he pa ien was unable o inges ca bohyd a e and did no ha e access o IV glucose o glucagon. E e y pa ien e alua ed by ou PH was adequa ely ea ed be o e a i - ing a he ED. Rega ding he use o hypoglycaemic d ugs, insulin seems o be he mos equen agen associa ed wi h se e e hypoglycaemia. Nine een pa ien s we e using sulphonylu eas and, amongs hem, 17 we e no using insulin. The equency o admission o he wa d o p olonged obse a ion was 31.1%, whils B acken idge [13] ound an admission a e o 11%. The e a e p obably egional di e - ences in c i e ia o admission o he wa d. The e is o en an associa ion wi h in e cu en illness which may also be a ac o esponsible o he ele a ed epo ed cos s o hypoglycaemia. Donnelly [8] also ound a high mo ali y a e se e e hypoglycaemia, which is sugges i e o i s alue as a p og- nos ic ac o . Despi e no being able o de e mine he cause o dea h, he high p e alence o se e e como bidi- ies in pa ien s su e ing se e e hypoglycaemia is o el- e ance [16]. Conclusions We ound ha many pa ien s a en’ adequa ely e alu- a ed and ea ed be o e being e e ed o he Eme gency Depa men . Hypoglycemia is a equen cause o eme - gency calls and only a mino i y hose is e alua ed in he Eme gency Depa men . Mos indi iduals e alua ed in his con ex use insulin. Table 3 Cha ac e iza ion o se e e hypoglycaemia epi- sodes eco ded in he Eme gency Depa men (n 61) Glycaemia (mg/dL) On si e: 38 ± 13.7 (3 below 20 mg/dL) Minimum–maximum: 20–68 ED a i al: 103 ± 80.5 Minimum–maximum: 20–349 Pa ien s e alua ed by ou PH: 202 ± 82.6 Glasgow coma scale All episodes: 14.0 (5.5–15.0) Noc u nal: 8.5 (3.0–15.0) Diu nal: 15.0 (13.5–15.0) Adminis a ion o ea men on si e Rela i e: 15 (24.6%) Heal h p o essional: 26 (42.6%) Type o ea men on si e (a ail- able in o ma ion in 24 cases) Hype onic glucose: 13 Pe os: 10 Glucagon: 1 Type o ea men in he ED 56 (91.8%) pa ien s ecei ed any kind o ea men Pe os: 2 Hype onic glucose: 23 (mean 2.2 ± 0.79 ials) Glucose 5–10% solu ion: 31 Maximal glycaemia du ing ED s ay (mmol/L) 256 ± 90.9 Minimum–maximum: 85–Hi Wo kup eques ed? Yes: 52 (85.2%) No: 9 (14.8%) Admission in he sho s ay uni Yes: 18 (29.5%) No: 43 (70.5%) ED s ay du a ion (h) 17.2 ± 1.27 Discha ge des ina ion Home: 40 (65.6%) O he acili y: 2 (3.3%) Wa d: 19 (31.1%) Page 5 o 5 Es e es e al. BMC Res No es (2018) 11:249 • as , con enien online submission • ho ough pee e iew by expe ienced esea che s in you ield • apid publica ion on accep ance • suppo o esea ch da a, including la ge and complex da a ypes • gold Open Access which os e s wide collabo a ion and inc eased ci a ions maximum isibili y o you esea ch: o e 100M websi e iews pe yea • A BMC, esea ch is always in p og ess. Lea n mo e biomedcen al.com/submissions Ready o submi you esea ch ? Choose BMC and bene i om: Limi a ions We ound a signi ican numbe o ED episodes wi h unspeci ied diagnosis, which may a bo a numbe o inco ec ly codi ied hypoglycaemia episodes. Episodes associa ed wi h speci ied consequences o hypoglycaemia may ha e been codi ied wi hou e e ence o hypoglycae- mia. We we e no able o de e mine he p e alence o use o speci ic insulin ea men egimens. Causes o hypo- glycaemia we e de e mined by he ea ing physician. These esul s may no be gene alizable o pa ien s om o he egions. Abb e ia ions T1DM: ype 1 diabe es melli us; T2DM: ype 1 diabe es melli us; PH: P e- hospi al Eme gency Uni ; ED: Eme gency Depa men ; SSU: Sho S ay Uni . Au ho s’ con ibu ions CE: s udy p o ocol, da a collec ion, s a is ical wo k, manusc ip ; CN, JJS and DC: s udy p o ocol, e iew o manusc ip . All au ho s ead and app o ed he inal manusc ip . Au ho de ails 1 Endoc inology, Diabe es and Me abolism Depa men , Cen o Hospi a- la São João, Alameda P o . He nani Mon ei o, 4200-319 Po o, Po ugal. 2 Facul y o Medicine, Uni e si y o Po o, Alameda P o . He nani Mon ei o, 4200-319 Po o, Po ugal. 3 Ins i u e o Resea ch and Inno a ion in Heal h, Po o, Po ugal. 4 Eme gency Depa men , Cen o Hospi ala São João, Po o, Po ugal. Acknowledgemen s Rui Baldaia, Eme gency Depa men , Cen o Hospi ala São João, o his con i- bu ion o acquisi ion o da a. These esul s we e pa ially published in he ollowing abs ac s: Es e es C, Ne es MC, Baldaia R, Sá J, Ca alho D: Cha ac e iza ion o he episodes o se e e hypoglycemia e alua ed by a P e-hospi al Ca e uni o a e e ence hospi al. Endoc ine Abs ac s, 2014;35:390. Es e es C, Ne es MC, Baldaia R, Sá J, Ca alho D: Cha ac e iza ion o se e e hypoglycemia episodes e alua ed in he Eme gency Depa men o a Cen al Hospi al. Endoc ine Abs ac s, 2014;35:389. Compe ing in e es s The au ho s decla e ha hey ha e no compe ing in e es s. A ailabili y o da a and ma e ials Con ac he co esponding au ho o ob ain access o he da ase . Consen o publica ion No applicable. E hics app o al and consen o pa icipa e The s udy p o ocol was app o ed by he E hics Comi ee o Cen o Hospi ala São João. Consen o pa icipa e no applicable. 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