Hemodynamic recovery after hypovolemic shock with lactated Ringer's and keratin resuscitation fluid (KRF), a novel colloid

Figures & data

Figure 1. Ultrasound Transit Flow Probes. A constant flow of 10 ml/min extracts blood from the carotid artery and returns it into the jugular vein. Saline injections into the venous line lowers blood density, which is detected by the venous flow probe and triggers automatic cardiac output measurement (Original Drawing).

Figure 2. Mean arterial pressure and heart rate monitoring. Hypotension was maintained for 30 minutes around 40 mmHg by periodically withdrawing blood.

Figure 3. Changes after hypovolemic shock and treatment with low-volume resuscitation fluids (Solid Line = KRF, Dashed Line = LR). A) Cardiac index, B) Stroke volume, C) Mean arterial pressure, D) Oxygen delivery.

Table I. Hemodynamics and arterial blood gases: low volume resuscitation, short term assessment.

	LR (n = 6)	KRF (n = 5)	Group	Time	Int.
CI (1/min/m^2)	10.81 ± 7.4	13.85 ± 11.6	0.26	0.0001	0.0001
SV (μl)	234.4 ± 16.5	261.5 ± 15	0.52	0.0001	0.15
Heart rate (bpm)	262 ± 19	292 ± 20	0.76	0.0001	0.33
MAP (mmHg)	58 ± 5	93 ± 6	0.003	0.0001	0.0001
ACV (ml)	12.1 ± 1.03	11.8 ± 1.3	0.73	0.0001	0.88
CBV (ml)	2.17 ± 0.1	2.35 ± 0.1	0.99	0.0001	0.01
pH	7.092 ± 0.02	7.161 ± 0.02	0.02	NA	NA
pCO2 (mmHg)	108.2 ± 7.3	89 ± 4	0.02	NA	NA
pO2	557.4 ± 12.6	619.9 ± 44	0.13	NA	NA
Base excess (mEq/L)	− 0.98 ± 1.4	− 0.38 ± 0.93	0.36	NA	NA
O2 delivery	18.6 ± 0.83	24.8 ± 2.3	0.15	0.0001	0.0003
Hematocrit	30.92 ± 0.6	32.4 ± 0.9	0.66	0.1	0.23
Vol. restoration*	0.32 ± 0.18	0.59 ± 0.17	0.16	NA	NA

Values presented were taken 120 minutes after treatment, refer to figures for changes over the 8 timepoints measured. All values represent mean and SEM. Group = main effect for group mean difference, Time = main effect for time mean difference, Int. = Interaction between group and time means.*Vol. Restoration: ml of ACV restored by every ml of resuscitation fluid infused IV.

Figure 4. Changes after hypovolemic shock and treatment with low-volume resuscitation fluids (Solid line = KRF, Dashed Line = LR). A) Actively Circulating Volume, B) Central Blood Volume.

Figure 5. Changes after hypovolemic shock and treatment with full-volume resuscitation fluids (Solid Line = KRF, Dashed Line = LR). A) Cardiac index, B) Stroke volume, C) Mean arterial pressure, D) Oxygen delivery.

Figure 6, Changes after hypovolemic shock and treatment with full-volume resuscitation fluids (Solid Line = KRF, Dashed Line = LR). A) Actively Circulating Volume, B) Central Blood Volume.

Table II. Hemodynamics and arterial blood gases: full volume resuscitation, short term assessment.

	LR (n = 5)	KRF(n = 5)	Group	Time	Int.
CI (1/min/m^2)	14.36 ± 2.3	13.15 ± 9	0.01	0.0001	0.005
SV (μl)	289.4 ± 3.1	261.9 ± 3	0.18	0.0001	0.01
Heart rate (bpm)	265 ± 29	283 ± 13	0.39	0.0001	0.07
MAP (mmHg)	77 ± 9	91 ± 4	0.01	0.0001	0.61
ACV (ml)	15.2 ± 1.6	17.2 ± 1.4	0.96	0.0001	0.002
CBV (ml)	2.54 ± 0.2	2.65 ± 0.3	0.42	0.0001	0.002
pH	7.100 ± 0.03	7.127 ± 0.06	0.35	NA	NA
pCO2 (mmHg)	107.3 ± 8.9	98.1 ± 15	0.32	NA	NA
pO2	634.6 ± 38	628.4 ± 57	0.47	NA	NA
Base excess (mEq/L)	− 0.75 ± 0.7	− 1.9 ± 0.3	0.16	NA	NA
O2 delivery	22.9 ± 3.8	23.7 ± 3.9	0.94	0.0001	0.37
Hematocrit	29.6 ± 1.6	31.7 ± 2.2	0.62	0.004	0.47
Vol. restoration*	0.13 ± 0.04	0.41 ± 0.09	0.01	NA	NA

Values presented were taken 120 minutes after treatment; refer to figures for changes over the 8 timepoints measured. All values represent mean and SEM. Group = main effect for group mean difference, Time = main effect for time mean difference, Int. = Interaction between group and time means. *Vol. Restoration: ml of ACV restored by every ml of resuscitation fluid infused IV.

Table III. Hemodynamics, arterial blood gases and electrolytes: long term assessment.

	Controls (n = 32)	LR (n = 7)	KRF (n = 9)	Sig.
CI (1/min/m^2)	19.53 ± 4.9	20.53 ± 12.4	20.36 ± 6.5	0.45
SV (μl)	314.4 ± 7.9	286 ± 9.8	331.9 ± 11.9	0.006
Heart rate (bpm)	332 ± 8	365 ± 16	335 ± 10	0.06
MAP (mmHg)	89 ± 1.5	96 ± 3.8	97 ± 3	0.91
ACV (ml)	18.1 ± 0.4	19.1 ± 1.2	20.8 ± 1.1	0.15
CBV (ml)	3.6 ± 0.1	3.61 ± 0.2	4 ± 0.2	0.09
CaO2 (ml)	NA	19.4 ± 0.3	19 ± 0.4	0.44
Myocardial O2 delivery	NA	10 ± 0.3	11.9 ± 0.5	0.006
pH	NA	7.34 ± 0.02	7.33 ± 0.01	0.65
PCO2 (mmHg)	NA	57.9 ± 2.1	58.1 ± 1.9	0.92
pO2	NA	584.7 ± 18.7	599.1 ± 26.6	0.67
Base excess (mEq/L)	NA	4.9 ± 0.7	4.3 ± 0.4	0.47
HCO3 (mEq/L)	NA	30.7 ± 0.6	30.3 ± 0.3	0.53
Na^+ (mEq/L)	NA	138.2 ± 0.8	137.8 ± 0.7	0.72
K^+ (mEq/L)	NA	4.19 ± 0.14	4.16 ± 0.09	0.88
iCa^+ (mEq/L)	NA	1.43 ± 0.01	1.46 ± 0.008	0.06
tHb (g/dL)	NA	12.6 ± 0.43	12.8 ± 0.25	0.67
Hematocrit	44.9 ± 0.3	37.2 ± 1.2	37.8 ± 0.7	0.68

All values represent mean and SEM. Sig. column represent t-test p value between LR and KRF. Healthy Control values are presented for reference purposes.

Figure 7. Tissue Histology. 5.1-5.2 Cardiac Muscle Histology. Endocardial simple squamous epithelium marked by black arrow, intercalated disk marked by white arrow, normal muscle striations are evidence throughout the tissue. 5.3-5.4 Renal Histology. Simple squamous epithelium (black arrow), Bowman space (B), glomerular basement membrane (white arrow tip), loop of Henle tubule (A) and proximal convoluted tubule (C), arterial pole (D). 5.5-5.6 Liver Histology. Portal triad composed of Portal vein (V), hepatic artery (black arrow) and bile duct (white arrow). 5.7-5.8 Brain Histology. Coronal cut through the medial thalamus (A) and surrounding third ventricle (B).