Hemodynamic effects of combined treatment with oxygen and hypertonic saline in hemorrhagic shock

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Hemodynamic effects of combined treatment with
oxygen and hypertonic saline in hemorrhagic shock

• Critical Care Medicine
• 2006 Nov 34(11)2784-91
• R ??? 95.12.05

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Introduction
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• Hallmark of the pathophysiology of hemorrhagic
  shockdecrease BP and organ perfusion ? marked
  and widespread impairment of tissue oxygenation
• Treatmentstop blood loss(replenish intravascular
  volume ), administer iv fluids (augment organ
  perfusion), and inhalation of oxygen (improve
  tissue oxygenation)

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• Choice of ideal resuscitation fluid in
  hemorrhagic shock ? debating
• Use of small volume resuscitation with
  hypertonic saline(HS) was initially advocated by
  Rocha e Silva and colleagues in the 1980s
• 4-5 mL/kg 7.5 NaCl marked ? in BP and CO,
  augmentation of peripheral organ perfusion, and
  favorable effect on the outcome after controlled
  hemorrhagic shock

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• A major part of the response is caused by the
  osmotic effect of HS on expansion of plasma
  volume, positive inotropic effect, induction of
  precapillary vasodilation, and reduction of
  tissue edema
• Recent studies showed HS attenuates postshock
  secondary systemic inflammatory reactions,
  restores the function of T cells, and reduces
  immunosuppression after hemorrhage

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• Ease of use in prehospital setting ? HS an
  attractive alternative to large volume
  resuscitation
• Difficulties in performing well-controlled
  prehospital trials, definite role in trauma
  patients ? ?

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• Inhalation of high concentrations O2 is routinely
  used in hemorrhagic shock ? augments O2 delivery
  and alleviate cellular hypoxia
• Limited information on the hemodynamic and
  cellular effects of O2 at high partial pressures
• Treatment with 100 O2 at 1 and 3 atmospheres
  given alone increases and maintains MABP,
  improves metabolic variables, attenuates
  microvascular fluid loss, improves survival rate
  and time in both short- and long-term models of
  severe controlled hemorrhage in rats

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• We also demonstrated in hemorrhagic shock that
  the inhalation of 100 O2 induces redistribution
  of blood flow from skeletal muscle to the
  splanchnic and renal vascular beds at the
  expense of skeletal muscle

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• The purpose of the present study was to evaluate
  combined hemodynamic effects of small volume
  resuscitation with hypertonic saline and
  inhalation of 100 oxygen in controlled
  hemorrhagic shock

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Materials and Methods
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• Male Sprague-Dawley rats (240-340g BW)
• Rats anesthetized with sodium pentobarbital
  (50mg/kg) intraperitoneally
• Catheter placed in right carotid a. for blood
  withdrawal and recording of MABP
• Left jugular vein for fluid infusion
• Tracheal cannulated

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• Midline lapa
• Isolate distal aorta and SMA
• Ultrasonic blood flow probe placed on distal
  aorta and on SMA
• Total microvascular blood flow to a loop of ileum
  and middle portion of gracilis muscle was
  assessed by a laser-Doppler blood flow meter
• All animal received heparin 800 u/kg
  intra-arterially ? inhibit coagulation of blood
  in experimental equipment

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• Induced hemorrhagic shock was by withdrawing 30
  of total blood volume (2mL/100g of BW) at
  constant rate within 90 min from carotid artery
  using withdrawal pump
• Sham shock rats underwent all surgical procedures
  but were not bled

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• A four stage experimental protocol
• 1. Bleeding90 mins
• 2. Follow-up and hemodynamic monitoring
• 20 mins (until time 110 mins)
• 3. Administration of NS (5mL/kg iv bolus)
• or HS (7.5 NaCl) 5mL/kg iv bolus
• at time 110 mins
• 4. Spontaneous inhalation of 100 O2
• through a mask-like device positioned
• around the tracheotomy tube for 90 mins
• (from time 115 mins to 205 mins)

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• Animals randomly assigned 5 groups underwent
  hemorrhagic shock and received posttreatment with
  
• (a) NS
• (b) NS oxygen
• (c) HS
• (d) HS oxygen
• (e) reversed order of treatment oxygen from
  time 110 mins HS at time 115 mins
• Sixth group of sham shock rats received HS
  oxygen

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• Blood sample were taken at time 0, 90, and 205
  mins

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Results
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Subsequent stabilization 62-70 mmHg
58-69 mmHg
HS Significant greater increase in MABP 52-55
mmHG, gradual decrease to value significantly
higher than NS group
Final MABP lower than beginning. Highest final
MABP value were HSoxygen, and NS the lowest
Inhalation of 100 oxygen induced an average
increase of 16-33 mmHg in MABP in sham, NS and HS
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• Group 6 received 100 oxygen at 110 mins, than
  infusion of HS at 115 mins.
• Result reversal of treatment did not influence
  the effect of combined treatment on MABP

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• Fig 2 absolute values and relative changes in
  vascular resistance in hindquarters, blood flow
  in distal aorta, and perfusion of gracilis muscle
  in thigh
• Effects of hemorrhage
• Immediate consequence of infusion of NaCl
• Acute effect o inhalation of oxygen

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Vascular resistance in NSoxygen, HS, and
HSoxygen groups significantly higher than after
bleeding
Vascular resistance in NS and HS groups higher
than after bleeding
Increase resistance in NSoxygen group higher
than NS, HS or HS oxygen
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?
DA blood flow in two HS groups higher than after
bleeding
Significant decrease after oxygen in the NS group
Decrease in DA flow in NS group after oxygen
Increase in DA flow after HS
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Decrease in muscle perfusion in NS group after
oxygen
Relative decrease in gracilis muscle perfusion in
NS oxygen group
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• In all hemorrhage groups, absolute values of
  final hindquarter vascular resistances were
  significantly higher, and distal aorta flow
  values were significantly lower
• Final absolute values of gracilis muscle
  perfusion were significantly higher in HS with
  oxygen group than in NS groups

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• Fig 3 absolute values and relative changes in
  resistance in SMA vascular bed, blood flow in
  SMA, and tissue perfusion of small bowel

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Decrease in SMA resistance after HS
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Increase in SMA flow after NS or HS
Increase in SMA flow in NS oxygen group
Higher SMA flow in NSoxygen, HS, and HSoxygen
Larger increase in SMA flow after HS and larger
increase in the two oxygen groups at the end
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Increase in intestinal perfusion after HS
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• End of experiments, SMA flows significantly lower
  than initial values in all hemorrhage groups, the
  two hemorrhage groups treated with oxygen
  maintained significantly higher SMA flow
• Highest final absolute values was detected in the
  hemorrhage HS oxygen group

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Enhanced transcapillary fluid shift
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_at_ transcapillary fluid shift _at_ hemodilution
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(No Transcript)
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Discussion
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• The present study was designed to evaluate
  combined hemodynamic effects of infusion of small
  volume HS and inhalation of 100 oxygen in the
  resuscitation of controlled hemorrhagic shock

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• Bolus infusion of small volume HS ? MABP, ?
  hindquarter vascular resistance, ? distal aorta
  blood flow
• Transiently ? SMA blood flow and augmented small
  bowel perfusion (splanchnic vascular bed)
• ? plasma osmolality , induced an expected
  transcapillary fluid shift into the vascular
  space, ( lower Hct and lower glucose and Cr), an
  important mechanism of its acute hemodynamic
  effect in hypovolemic shock

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• Inhalation of 100 oxygen after infusion of small
  volume NS ? rapid increase in MABP
• oxygen-induced decrease in distal aorta blood
  flow and gracilis muscle perfusion.
• O2 did not change SMA vascular resistance and
  increased SMA flow.

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• It increased resistance in skeletal muscle, ?
  blood flow to the hindquarter, raised arterial
  blood pressure.
• The combination of increased blood pressure and
  the differential effect on regional vascular
  resistances caused redistribution of blood flow
  to the lower resistance splanchnic vascular bed
  at the expense of skeletal muscle

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• HS prevented an oxygen-induced decrease in distal
  aorta blood flow and gracilis muscle perfusion.
• Combination of HS and O2 maintained MABP at
  slightly higher values and SMA flow at
  significantly higher values, prevents O2 induced
  decrease in blood flow to the hindquarters.
• Results combined use of HS and oxygen amends
  some of the shortcomings of each treatment alone
  (e.g., the transient nature of HS-induced
  hemodynamic effects and the vasoconstrictor
  effect of hyperoxia in skeletal muscle), improves
  splanchnic perfusion without compromising the
  hindquarter vascular bed.

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• Combined fluid and O2 therapy yielded the most
  significant beneficial effect on final blood
  lactate concentrations ? attributed to improved
  tissue oxygenation.

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• Splanchnic ischemia occurs early in shock
  deprivation of vital nutrients (oxygen)
• Our findings support a suggestion that rapid
  combined use of HS and hyperoxia during early
  resuscitative stages of trauma that restores
  blood volume, increases blood pressure, and
  augments both visceral blood flow and oxygen
  delivery also ameliorates splanchnic (and
  possibly other organs) hypoxia.

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• Beneficial effects of hyperoxia after hemorrhage
  should be weighed against some alleged and
  potential deleterious consequences.
• The commonly accepted paradigm of
  ischemia/reperfusion injury emphasizes a central
  role for oxygen-derived free radical formation in
  activation of the inflammatory cascade

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• Evidence from studies supports a protective role
  of hyperoxia in ischemia/reperfusion
• Hyperoxia exert a simultaneous ameliorating
  effect on a number of steps in the
  proinflammatory cascade after ischemia/reperfusion
  , including interference with neutrophil adhesion
  and free radical production
• Hyperoxia also exert indirect effects on the
  inflammatory response by ameliorating tissue
  hypoxia a key trigger of inflammation.
• Prolonged use of oxygen at high partial pressures
  exposes patients to its potential toxic effects
  (e.g., pulmonary oxygen toxicity).

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• The results may be looked at as representing a
  clinically relevant short-term hemodynamic
  outcome after controlled bleeding
• Short-term models of hemorrhage and resuscitation
  in the present study do not provoke a significant
  immediate systemic inflammatory response
• The favorable acute hemodynamic effects of
  combined treatment with hypertonic saline and
  oxygen may exert beneficial effects on longterm
  consequences and the outcome of controlled
  hemorrhagic shock.

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Conclusions
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• Early combined use of HS and oxygen exerts a
  favorable extended profile of hemodynamic
  effects that augments and sustains some of the
  important beneficial isolated effects of HS
  (e.g., increased blood pressure and increased
  blood flow to the splanchnic bed) by the addition
  of hyperoxia and at the same time diminishes some
  undesired hemodynamic effects of hyperoxia alone
  (e.g., decreased flow to skeletal muscle)