Unintended consequences

Fluid resuscitation worsens shock in an ovine model of endotoxemia

Liam Byrne, Nchafatso G. Obonyo, Sara D. Diab, Kimble R. Dunster, Margaret R. Passmore, Ai Ching Boon, Louise See Hoe, Sanne Pedersen, Mohd Hashairi Fauzi, Leticia Pretti Pimenta, Frank Van Haren, Christopher M. Anstey, Louise Cullen, John Paul Tung, Kiran Shekar, Kathryn Maitland, John F. Fraser

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Rationale: Fluid resuscitation is widely considered a life-saving intervention in septic shock; however, recent evidence has brought both its safety and efficacy in sepsis into question. Objectives: In this study, we sought to compare fluid resuscitation with vasopressors with the use of vasopressors alone in a hyperdynamic model of ovine endotoxemia. Methods: Endotoxemic shock was induced in 16 sheep, after which they received fluid resuscitation with 40 ml/kg of 0.9% saline or commenced hemodynamic support with protocolized noradrenaline and vasopressin. Microdialysis catheters were inserted into the arterial circulation, heart, brain, kidney, and liver to monitor local metabolism. Blood samples were recovered to measure serum inflammatory cytokines, creatinine, troponin, atrial natriuretic peptide, brain natriuretic peptide, and hyaluronan. All animals were monitored and supported for 12 hours after fluid resuscitation. Measurements and Main Results: After resuscitation, animals that received fluid resuscitation required significantly more noradrenaline to maintain the same mean arterial pressure in the subsequent 12 hours (68.9 mg vs. 39.6 mg; P = 0.04). Serum cytokines were similar between groups. Atrial natriuretic peptide increased significantly after fluid resuscitation compared with that observed in animals managed without fluid resuscitation (335 ng/ml [256-382] vs. 233 ng/ml [144-292]; P = 0.04). Cross-sectional time-series analysis showed that the rate of increase of the glycocalyx glycosaminoglycan hyaluronan was greater in the fluid-resuscitated group over the course of the study (P = 0.02). Conclusions: Fluid resuscitation resulted in a paradoxical increase in vasopressor requirement. Additionally, it did not result in improvements in any of the measured microcirculatory- or organspecific markers measured. The increase in vasopressor requirement may have been due to endothelial/glycocalyx damage secondary to atrial natriuretic peptide-mediated glycocalyx shedding.

Original languageEnglish
Pages (from-to)1043-1054
Number of pages12
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume198
Issue number8
DOIs
Publication statusPublished - 15 Oct 2018

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Endotoxemia
Resuscitation
Shock
Sheep
Glycocalyx
Atrial Natriuretic Factor
Hyaluronic Acid
Norepinephrine
Cytokines
Troponin
Brain Natriuretic Peptide
Microdialysis
Septic Shock
Glycosaminoglycans
Serum
Vasopressins
Creatinine
Sepsis
Arterial Pressure
Catheters

Cite this

Byrne, L., Obonyo, N. G., Diab, S. D., Dunster, K. R., Passmore, M. R., Boon, A. C., ... Fraser, J. F. (2018). Unintended consequences: Fluid resuscitation worsens shock in an ovine model of endotoxemia. American Journal of Respiratory and Critical Care Medicine, 198(8), 1043-1054. https://doi.org/10.1164/rccm.201801-0064OC
Byrne, Liam ; Obonyo, Nchafatso G. ; Diab, Sara D. ; Dunster, Kimble R. ; Passmore, Margaret R. ; Boon, Ai Ching ; Hoe, Louise See ; Pedersen, Sanne ; Fauzi, Mohd Hashairi ; Pimenta, Leticia Pretti ; Van Haren, Frank ; Anstey, Christopher M. ; Cullen, Louise ; Tung, John Paul ; Shekar, Kiran ; Maitland, Kathryn ; Fraser, John F. / Unintended consequences : Fluid resuscitation worsens shock in an ovine model of endotoxemia. In: American Journal of Respiratory and Critical Care Medicine. 2018 ; Vol. 198, No. 8. pp. 1043-1054.
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abstract = "Rationale: Fluid resuscitation is widely considered a life-saving intervention in septic shock; however, recent evidence has brought both its safety and efficacy in sepsis into question. Objectives: In this study, we sought to compare fluid resuscitation with vasopressors with the use of vasopressors alone in a hyperdynamic model of ovine endotoxemia. Methods: Endotoxemic shock was induced in 16 sheep, after which they received fluid resuscitation with 40 ml/kg of 0.9{\%} saline or commenced hemodynamic support with protocolized noradrenaline and vasopressin. Microdialysis catheters were inserted into the arterial circulation, heart, brain, kidney, and liver to monitor local metabolism. Blood samples were recovered to measure serum inflammatory cytokines, creatinine, troponin, atrial natriuretic peptide, brain natriuretic peptide, and hyaluronan. All animals were monitored and supported for 12 hours after fluid resuscitation. Measurements and Main Results: After resuscitation, animals that received fluid resuscitation required significantly more noradrenaline to maintain the same mean arterial pressure in the subsequent 12 hours (68.9 mg vs. 39.6 mg; P = 0.04). Serum cytokines were similar between groups. Atrial natriuretic peptide increased significantly after fluid resuscitation compared with that observed in animals managed without fluid resuscitation (335 ng/ml [256-382] vs. 233 ng/ml [144-292]; P = 0.04). Cross-sectional time-series analysis showed that the rate of increase of the glycocalyx glycosaminoglycan hyaluronan was greater in the fluid-resuscitated group over the course of the study (P = 0.02). Conclusions: Fluid resuscitation resulted in a paradoxical increase in vasopressor requirement. Additionally, it did not result in improvements in any of the measured microcirculatory- or organspecific markers measured. The increase in vasopressor requirement may have been due to endothelial/glycocalyx damage secondary to atrial natriuretic peptide-mediated glycocalyx shedding.",
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Byrne, L, Obonyo, NG, Diab, SD, Dunster, KR, Passmore, MR, Boon, AC, Hoe, LS, Pedersen, S, Fauzi, MH, Pimenta, LP, Van Haren, F, Anstey, CM, Cullen, L, Tung, JP, Shekar, K, Maitland, K & Fraser, JF 2018, 'Unintended consequences: Fluid resuscitation worsens shock in an ovine model of endotoxemia', American Journal of Respiratory and Critical Care Medicine, vol. 198, no. 8, pp. 1043-1054. https://doi.org/10.1164/rccm.201801-0064OC

Unintended consequences : Fluid resuscitation worsens shock in an ovine model of endotoxemia. / Byrne, Liam; Obonyo, Nchafatso G.; Diab, Sara D.; Dunster, Kimble R.; Passmore, Margaret R.; Boon, Ai Ching; Hoe, Louise See; Pedersen, Sanne; Fauzi, Mohd Hashairi; Pimenta, Leticia Pretti; Van Haren, Frank; Anstey, Christopher M.; Cullen, Louise; Tung, John Paul; Shekar, Kiran; Maitland, Kathryn; Fraser, John F.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 198, No. 8, 15.10.2018, p. 1043-1054.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Unintended consequences

T2 - Fluid resuscitation worsens shock in an ovine model of endotoxemia

AU - Byrne, Liam

AU - Obonyo, Nchafatso G.

AU - Diab, Sara D.

AU - Dunster, Kimble R.

AU - Passmore, Margaret R.

AU - Boon, Ai Ching

AU - Hoe, Louise See

AU - Pedersen, Sanne

AU - Fauzi, Mohd Hashairi

AU - Pimenta, Leticia Pretti

AU - Van Haren, Frank

AU - Anstey, Christopher M.

AU - Cullen, Louise

AU - Tung, John Paul

AU - Shekar, Kiran

AU - Maitland, Kathryn

AU - Fraser, John F.

PY - 2018/10/15

Y1 - 2018/10/15

N2 - Rationale: Fluid resuscitation is widely considered a life-saving intervention in septic shock; however, recent evidence has brought both its safety and efficacy in sepsis into question. Objectives: In this study, we sought to compare fluid resuscitation with vasopressors with the use of vasopressors alone in a hyperdynamic model of ovine endotoxemia. Methods: Endotoxemic shock was induced in 16 sheep, after which they received fluid resuscitation with 40 ml/kg of 0.9% saline or commenced hemodynamic support with protocolized noradrenaline and vasopressin. Microdialysis catheters were inserted into the arterial circulation, heart, brain, kidney, and liver to monitor local metabolism. Blood samples were recovered to measure serum inflammatory cytokines, creatinine, troponin, atrial natriuretic peptide, brain natriuretic peptide, and hyaluronan. All animals were monitored and supported for 12 hours after fluid resuscitation. Measurements and Main Results: After resuscitation, animals that received fluid resuscitation required significantly more noradrenaline to maintain the same mean arterial pressure in the subsequent 12 hours (68.9 mg vs. 39.6 mg; P = 0.04). Serum cytokines were similar between groups. Atrial natriuretic peptide increased significantly after fluid resuscitation compared with that observed in animals managed without fluid resuscitation (335 ng/ml [256-382] vs. 233 ng/ml [144-292]; P = 0.04). Cross-sectional time-series analysis showed that the rate of increase of the glycocalyx glycosaminoglycan hyaluronan was greater in the fluid-resuscitated group over the course of the study (P = 0.02). Conclusions: Fluid resuscitation resulted in a paradoxical increase in vasopressor requirement. Additionally, it did not result in improvements in any of the measured microcirculatory- or organspecific markers measured. The increase in vasopressor requirement may have been due to endothelial/glycocalyx damage secondary to atrial natriuretic peptide-mediated glycocalyx shedding.

AB - Rationale: Fluid resuscitation is widely considered a life-saving intervention in septic shock; however, recent evidence has brought both its safety and efficacy in sepsis into question. Objectives: In this study, we sought to compare fluid resuscitation with vasopressors with the use of vasopressors alone in a hyperdynamic model of ovine endotoxemia. Methods: Endotoxemic shock was induced in 16 sheep, after which they received fluid resuscitation with 40 ml/kg of 0.9% saline or commenced hemodynamic support with protocolized noradrenaline and vasopressin. Microdialysis catheters were inserted into the arterial circulation, heart, brain, kidney, and liver to monitor local metabolism. Blood samples were recovered to measure serum inflammatory cytokines, creatinine, troponin, atrial natriuretic peptide, brain natriuretic peptide, and hyaluronan. All animals were monitored and supported for 12 hours after fluid resuscitation. Measurements and Main Results: After resuscitation, animals that received fluid resuscitation required significantly more noradrenaline to maintain the same mean arterial pressure in the subsequent 12 hours (68.9 mg vs. 39.6 mg; P = 0.04). Serum cytokines were similar between groups. Atrial natriuretic peptide increased significantly after fluid resuscitation compared with that observed in animals managed without fluid resuscitation (335 ng/ml [256-382] vs. 233 ng/ml [144-292]; P = 0.04). Cross-sectional time-series analysis showed that the rate of increase of the glycocalyx glycosaminoglycan hyaluronan was greater in the fluid-resuscitated group over the course of the study (P = 0.02). Conclusions: Fluid resuscitation resulted in a paradoxical increase in vasopressor requirement. Additionally, it did not result in improvements in any of the measured microcirculatory- or organspecific markers measured. The increase in vasopressor requirement may have been due to endothelial/glycocalyx damage secondary to atrial natriuretic peptide-mediated glycocalyx shedding.

KW - Endotoxemia

KW - Fluid resuscitation

KW - Sepsis

KW - Septic shock

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U2 - 10.1164/rccm.201801-0064OC

DO - 10.1164/rccm.201801-0064OC

M3 - Article

VL - 198

SP - 1043

EP - 1054

JO - American Review of Respiratory Disease

JF - American Review of Respiratory Disease

SN - 1073-449X

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