Appendix. Supplementary figures and tables
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1 This appendix was part of the submitted manuscript and has been peer reviewed. It is posted as supplied by the authors. Appendix. Supplementary figures and tables Figure A1. Flowchart describing patient selection process
2 Figure A2. Changes in MAP with different fluid bolus volume in the whole cohort. A positive value on the Yaxis indicates a rise in blood pressure 60 Change in MAP after before fluid bolus (mmhg) Bolus amount (mls) r = 0.16; r2 = 0.024; p<0.05
3 Figure A3. Changes in MAP with different fluid bolus volume in patients that were hypotensive or severly hypotensive on arrvial to the ED. A positive value indicates a rise in blood pressure Change in MAP after before fluid bolus (mmhg) y = *x; r = ; p = ; r 2 = Bolus amount (mls)
4 Figure A4. Changes in mean arterial pressure (MAP) in patients treated with noradrenaline (NA) on arrival to the ED, prior and after the commencement of the NA infusion. The MAP increased after the start of the NA infusion (p> Mean arterial pressure (mmhg) ** Before vs. after NE 0 MAP on arrival Before NA administration After NA administration
5 Figure A5. Changes in systolic arterial pressure (SAP) in patients who were hypotensive (H) on arrival (SBP < 100 mmhg; H); patients who were severely hypotensive (S) on arrival (SBP < 90 mmhg; S); patients who became hypotensive (NH) and patients who became severely hypotensive (NS) during the first six hours after arrival to the emergency department. Changes are depicted in a box plot. Box: mean ± SE; whisker: mean ± 0.95 confidence interval 140 Systolic arterial pressure (mmhg) Time (h) SAP H SAP S SAP NH SAP NS
6 Figure A6. Scatterplot of the total fluid during the first six hours after arrival to the emergency department and the change in mean arterial pressure during the same period in severely hypotensive patients. A positive value on the Yaxis indicates a rise in blood pressure Change in MAP from arrival to the ED to 6 hours later (mmhg) Patients with SBP<90 mmhg on arrvial r=0.52; p<0.05; r 2 = Total fluid volume during the first six hours after arrival to the ED (mls)
7 Table A1. Characteristics of full study cohort and patients receiving fluid bolus therapy All ED patients screened Diagnosis and diagnosis codes Gastroenteritis and colitis of unspecified origin (A09.9) Number of cases scanned Number of patients included 30 3 Perforation of oesophagus (K22.3) 2 0 Urinary tract infection (N39.0) Acute abdomen (R10.0) 9 0 Bronchopneumonia, unspecified (J18.0) 12 1 Lobar pneumonia, unspecified (J18.1) 9 1 Acute bronchitis, unspecified (J20.9) 4 0 Acute bronchitis, unspecified (J22) Pneumonitis due to food and vomit (J69.0) Other specified sepsis (A41.8) Sepsis, unspecified (A41.9) Bacterial infection, unspecified (A49.9) 8 2 Fluid bolus treated patients Comorbidities No. of observations (in 101 cases) Heart failure 17 Coronary artery disease 17 CODP 15 Diabetes mellitus 12 HIV 0 Hypertension 34 Liver failure 8 History of malignancy 20 Neurological disease 23 History of smoking 35 Sepsis details 50 Urinary sepsis 12 Peritonitis 2 Other intraabdominal processes 15 Abscess in extremities 2 Other causes of sepsis 22 Severe sepsis 75 Septic shock 36 Positive blood culture 18 Antibiotics given within 6 hours from arrival in the emergency department 83
8 Table A2. Vital signs in different subgroups. Hypotensive patients vs. severely hypotensive patients during the first 6 hours Crystalloids Colloids Packed red cells Fresh frozen plasma Platelets Fraction of inspired O 2 Body temperature ( C) Heart rate (x min1) Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) Mean arterial pressure (mmhg) Hypotensive patients n=25 Severely hypotensive patients On arrival 2 hours 4 hours 6 hours On arrival 2 hours 4 hours 6 hours 0.21( ) 500(05000) 0(00) 580(0 1720) 340(0 750) 500(0 2000) 460(0 700) 785(05000) n=21 480(0 1460) 490(0 1350) 0(0500) 0(0750) 0(0600) 0(00) 00(00) 50(0150) 0(00) 0(00) 0(0150) 0(00) 00(00) 30(0180) 0(00) 0(00) 0(0180) 0(00) 0(0750) 0(0700) 0(00) 0(00) 0(00) 0.21( ) 0.21( ) 0.21( ) 0.21( ) 0.21( ) 0.30( ) 0.28( ) 37.4± ± ± ±1.2* 37.1± ± ± ± ±25 93±23 90±19 88±21 104±27 97±26 96±21 92±20 106±23*** 105±17 104±15* 103±17 78±11 97±10 95±13 100±21 65±14*** 61±10* 59±12 59±15* 45±8 53±8 53±11 54±12 71±5*** 73±10* 75±16* 76±17 56±8 68±8 66±9 70±14 Respiratory rate (x min 1 ) 18(1623) 18(1622) 18(1622) 18(1622) 18(1620) 19(1822) 18(1620) 18(1820) Arterial SaO 2 98(96 98(97 99(97 98(97 97(9499) 98(97100) 97(9499) 99(97100) 100) 100) 100) 100) Arterial ph 7.37± ± ± ± ± ± ± ±0.06 Arterial PaO 2 (mm Hg) 87±66 151± ±76 113±42 32±11 53±35 115±87 112±36 Arterial PaCO 2 (mm 42±11 40±13 37±4 37±6 42±10 39±9 37±2 40±6 Hg) base excess 1.6± ± ± ± ± ± ± ±4.8 (mmol x l 1 ) lactate 2.0( ( ( ( ( (1.6 (mmol x litre 2.1(1.53.1) 1.8(1.53.0) 2.4) 3.2) 2.3) 3.0) 2.8) 2.8) 1 ) Blood haemoglobin 124±24 122±22 113±22 120±20 115±28 118±22 96±26 123±18 (g x l 1 ) chloride 101±5 102±6 102±7 103±6 100±5 102±4 98±6 104±3 (mmol x l 1 ) 129(71 140(72 123(90 75(5794) 142(85 161(131 20(2020) 90(77
9 creatinine (µmol x l 1 ) Albumin (g x l 1 ) 149) 160)* 150) 216) 182) 103) 33±6 32±7 31±5 26±11 30±8 28±6 R Range *p<0.05 ***p<0.001
10 Table A3. Vital signs in different subgroups. Survivors vs. nonsurvivors patients during the first 6 hours On arrival Survivors at 28 days n=75 2 hours 4 hours 6 hours On arrival Nonsurvivors at 28 days n=26 2 hours 4 hours 6 hours Crystalloids 500(0 580(0 500(0 500(0 500(0 400(0 5000) R 1720) R 2000) R 1750) R 1500) R 2500) R Colloids 0(00) R 0(0750) R 0(0700) R 0(0500) R 0(0620) R 0(0500) R Packed red cells 0(00) R 0(00) R 0(0150) R 0(00) R 0(00) R 0(0150) R Fresh frozen plasma 0(00) R 0(00) R 0(0180) R 0(00) R 0(00) R 0(0300) R Platelets 0(00) R 0(00) R 0(0200) R 0(00) R 0(00) R 0(00) R Fraction of inspired O ( ) 0.21( )** 0.21( )** 0.21( ) 0.28( ) 0.28( ) 0.32( ) 0.32( ) Body temperature ( C) 37.4± ± ± ±1.2** 37.2± ± ± ±0.6 Heart rate (x min1) 103±25* 93±23* 90±19** 88±21*** 118±31 108±28 104±22 102±21 Systolic blood pressure (mm 106±23 105±17 104±15 103±17 99±21 102±25 100±20 99±20 Hg) Diastolic blood pressure (mm 65±14** 61±10 59±12** 59±15 55±16 57±15 53±16 56±13 Hg) Mean arterial pressure (mmhg) 78±16* 76±11 74±11** 74±14 69±17 73±14 68±15 71±11 Respiratory 18(16 18(16 18(16 rate (x min 1 ) 23)** 22)*** 22)** 18(1622) 23(2028) 24(1928) 20(1925) 19(1823) Arterial SaO 2 98(97 98(96 98(97 97(9499) 100)* 100) 100)* 97(9499) 97(9599) 97(9699) 97(9698) Arterial ph 7.37± ± ± ± ± ± ± ±0.17 Arterial PaO 2 (mm Hg) 87±66 151± ±76 113±42 73±77 47±15 102±67 107±68 Arterial PaCO 2 (mm Hg) 42±11 40±13* 37±4 37±6* 47±18 53±22 49±13 48±19 base excess (mmol x l 1 ) 1.6± ± ± ± ± ± ± ±6.3 lactate 2.0( ( ( ( ( ( (1.5 (mmol x litre 1 1.8(1.53.6) ) 2.4) 3.1) 3.2) 2.3) 2.9) 7.0) 4.7) Blood haemoglobin (g x l 1 ) 124±24 122±22 113±22 120±20 119±23 121±24 121±23 114±21 White blood 11.5( ( ( ( ( ( ( (10.4 cell count (x ) 16.9) 21.1) 15.6) 15.5) 16.7) 16.6) 10.8) ) sodium (mmol 134±5 135±4 133±5 133±5 135±6 135±6 134±5 135±5 x l 1 ) potassium 4.1± ±0.6* 4.1± ±0.7* 4.4± ± ± ±0.7
11 (mmol x l 1 ) chloride (mmol x l 1 ) creatinine (µmol x l 1 ) Albumin (g x l 1 ) 101±5 102±6 102±7 103±6 101±5 102±5 103±5 106±6 107(71 149) 129(72 160) 148(90 150) 77(5794) 146(84 197) 150(85 162) 116(38 194) 103(77 274) 33±6 32±7 31±5 26±11 29(2232) 32(2938) 26(2626) 23(1827) R Range *p<0.05 ***p<0.001
12 Table A4. Mortality in severely hypotensive patients at 6 hours (i.e. the failed early resuscitation group vs. the rest) BP at 6h Alive at 28 days Count Percent Severely hypotensive at 6h Y N 5 29 Normotensive at 6h Y N Hypotensive at 6 h Y Missing data Y 5 No difference between mortality ratios. N 7 20
13 Table A5. Physiological changes over time in the hypotensive on arrival, severely hypotensive on arrival, hypotensive in the ED, severely hypotensive in the ED groups Group based on timing of hypotension Hypotensive on arrival Severely hypotensive on arrival Normotensive on arrival, hypotensive later Normotensive on arrival, severely hypotensive later n Mortality at 30 days (%) h 6h 0h 6h 0h 6h 0h 6h Crystalloids 1700(22 0 Colloids Packed red cells Fresh frozen plasma Platelets Fraction of inspired O ( ) R 1200( ) R 3670) R 0(0 200) R 0(0 1370) R 0(00)R 0(00) R 0(00) R 1350( ) R 0(0 1000) R 0(0 180) R 0(00)R 0(0150) 0(0 150) R 0(00)R 0(0300) 0(00) R 0(00) R 0(00) R 0(0200) 0.21( ) 0.28( ) 0.21( ) 0.28( ) 36.3± ( ) 0.21( ) 36.6± ( ) 0.25( ) Body 37.0± ±1.6 temperature ( C) ± ± ± ±0.8 Heart rate (x min 1) 104±29 96±20 104±27 92±20 110±15 92±25 108±32 89±22 Systolic blood pressure (mm Hg) 95±4 104±24 78±11 100±21 124±19 102±10 118±17 102±16 Diastolic blood pressure (mm Hg) 54±8 62±16 45±8 54±12 67±11 59±11 74±14 59±16 Mean arterial pressure (mmhg) 71±5 76±17 56±8 70±14 86±10 73±9 88±14 73±13 Respiratory rate 20(16 20(18 18(16 18(18 19(17 19(17 18(16 (x min 1 21(1828) ) 24) 22) 20) 20) 26) 24) 23) Arterial SaO 2 97(94 98(96 97(94 98(97 97(94 98(97 98(94 97(96 98) 100) 99) 100) 99) 99) 100) 99) Arterial ph 7.40± ± ± ± ± ± ± Arterial PaO 2 (mm Hg) 104±71 112±36 133±111 93±52 102±29 Arterial PaCO 2 (mm Hg) 41±8 39±11 42±9 40±6 46±17 46±16 41±15 base excess (mmol x l 1.4± ± ± ±4.8 ) 0.5± ± ±3.9 lactate (mmol/litre) Blood haemoglobin (g x l 1 ) White blood cell count (x 10 9 ) sodium (mmol x l 1 ) potassium (mmol x l 1 ) 2.1( ) 1.8( ) 2.3( ) 2.0( ) 1.3( ) 2.0( ) 1.7( ) 123±20 110±17 115±28 123±18 129±25 123±22 116± ( ) 12.4( ) 9.6(7.4 17) 10.9( ) 135±5 132±5 132±5 133±3 135±6 135±4 134±5 4.0± ± ± ± ± ± ±0.5
14 chloride (mmol x l 1 ) creatinine (µmol x l 1 ) Albumin (g x l 1 ) R Range 101±6 101±7 100±5 104±3 100±5 102±5 105±5 107(72 133) 142(85 216) 107±46 138(65 160) 32±6 30±8 32±7 33±6
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