British Journal of Anaesthesia, 2003, Vol. 91, No. 2 224-232
© 2003 The Board of Management and Trustees of the British Journal of Anaesthesia
Laboratory Investigations |
Effects of sustained post-traumatic shock and initial fluid resuscitation on extravascular lung water content and pulmonary vascular pressures in a porcine model of shock
,21 MRC Trauma Group University of Manchester, University of Manchester, Oxford Road, Manchester M13 9PT, UK. 2 South Manchester University Hospitals, Manchester, UK.
Corresponding author: University Department of Anaesthesia and Intensive Care, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK. E-mail: mahesan.nirmalan@man.ac.uk Declaration of interest: Dr D. J. Edwards acted as a Medical Advisor to Maelor Pharmaceuticals, Ltd.
Accepted for publication: March 6, 2003
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Abstract |
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Background. The temporal evolution of lung injury following post-traumatic shock is poorly understood. In the present study we have tested the hypothesis that manifestations of pulmonary vascular dysfunction may be demonstrable within the first hour after the onset of shock.
Methods. Twenty-nine anaesthetized pigs (mean weight 27.4 kg; (SD) 3.2) were randomly allocated to three groups: control (C, n=9), shock resuscitated with either NaCl 0.9% (S, n=10), or 4% gelatine (G, n=10). Shock was maintained for 1 h followed by fluid resuscitation with either normal saline or 4% gelatine solution. Cardiac output (CO), mean arterial pressure (MAP), mixed venous saturation (SvO2), blood lactate concentration, mean pulmonary artery pressure (MPAP), MPAP/MAP, pulmonary vascular resistance (PVR), extravascular lung water index (EVLWi), PaO2/FIO2, venous admixture (Q·S/Q·T), and dynamic lung compliance (Cdyn) were measured at baseline, beginning of shock phase, end of shock phase, and post-resuscitation.
Results. At the end of volume resuscitation CO was restored to control values in both shock groups. MAP remained significantly below control values (95% CI: C=70–95, S=28–52, G=45–69 mm Hg) in both shock groups. MPAP/MAP was significantly greater in both shock groups at the end of the shock phase (95% CI; C=0.15–0.24, S=0.28–0.38, G=0.32–0.42) and at the post-resuscitation phase (95% CI: C=0.12–0.30, S=0.43–0.61, G=0.32–0.49) indicating the presence of relative pulmonary hypertension. This was associated with a significant increase in PVR in Group S (F=3.9; P<0.05). There were no significant changes in PaO2/FIO2, Q·S/Q·T, EVLWi, or Cdyn. In a small cohort of animals a measurable increase in EVLWi (>30%) and reduction in Cdyn (>10%) were observed.
Conclusions. Pulmonary vascular injury manifesting as relative pulmonary hypertension and increased PVR may occur within the first hour after the onset of shock. These changes may not be accompanied by overt changes in oxygenation, compliance, or EVLWi.
Br J Anaesth 2003; 91: 224–32
Keywords: complications, pulmonary hypertension; complications, pulmonary vascular resistance; complications, shock; lung, functions; lung, water
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Introduction |
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In what is now widely regarded as a landmark publication Cournand, Riley and co-workers in 1943 first demonstrated that patients with untreated post-traumatic shock were characterized by reductions in circulating blood volume, cardiac output (CO), and oxygen delivery.1 Some of the subjects in this initial study had reduced arterial oxygen saturation (<85%) even in the absence of direct pulmonary trauma. Subsequently, Brewer and colleagues in 1946 described the condition ‘wet lungs’ among war casualties on initial admission to forward field hospitals.2 Since these two initial reports, early changes in lung function as a result of shock have drawn considerable attention. Holcroft and co-workers,3 Noble,4 and Sturm and colleagues5 have demonstrated that an increase in extravascular lung water content (EVLW) may be demonstrated in laboratory models of shock. Even though the underlying causes for early increases in EVLW remain unproven intestinal translocation of endotoxin brought about by hepato-splanchnic ischaemia and the consequent activation of inflammatory cascades may provide a potential explanation.6 7 Similar changes in pulmonary function have been explored in greater detail in laboratory models of sepsis where sequestration of leukocytes and impaired endothelial function has been demonstrated within the first 4 h after exposure to endotoxin.8 9
The importance of these pathophysiological processes to the initial clinical presentation of patients following a period of sustained post-traumatic shock is not known. Hypo xaemia is a common finding in such patients even in the absence of direct chest trauma and consequently the routine administration of oxygen is recommended in the Advanced Trauma Life Support protocols.10 While ventilation/perfusion mismatch, aspiration of gastric contents and fluid overload during initial fluid resuscitation are considered possible causes, shock mediated endothelial changes are rarely considered important at this very early stage. Characterizing the role of shock per se on pulmonary function, however, is important in order to initiate appropriate therapies for these patients. For example, observed increases in EVLW (manifesting as hypoxaemia associated with pulmonary oedema or fine basal crepitations over the lung fields) when wrongly attributed to iatrogenic fluid overload frequently leads to fluid restriction or even the use of diuretics with potentially serious consequences in patients who are already volume depleted. The choice of resuscitation fluids continues to draw considerable interest and debate amongst critical care physicians in this context. This is particularly relevant in the light of three recent meta analyses that showed conflicting results on the choice of resuscitation fluids on clinical outcome.11–13 The current clinical consensus, however, is that the choice of resuscitation fluids does not influence the immediate or long-term pulmonary outcome in patients with post-traumatic shock.14 15 In the light of these uncertainties we undertook the following study in a laboratory model of sustained post-traumatic shock to test the following hypotheses.
Primary hypotheses
A combination of standardized skeletal injury followed by a period (1 h) of acute hypovolaemic shock in the anaesthetized pig may reproduce the physiological abnormalities consistent with those described in human victims of post-traumatic shock and thereby be of relevance in the study of pulmonary changes in shock.
That in such a model an increase in EVLW and other features of pulmonary vascular dysfunction are demonstrable before fluid resuscitation is commenced and these changes continue to be an integral component of the overall pathophysiological profile even after initial volume replacement.
Secondary hypothesis
The nature of fluids (crystalloids or colloids) used in initial resuscitation does not influence early changes in EVLW content or other pulmonary functions.
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Methods |
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With University Ethics Committee approval, 29 immature female Large-White pigs (mean weight 27.4 (SD 3.2) kg) were randomly allocated to a control group (C, n=9), a shock group resuscitated with NaCl 0.9% (S, n=10) and a shock group resuscitated with succinylated gelatine solution 4% (Maelor Pharmaceuticals Ltd, Wrexham, UK) (G, n=10). Anaesthesia was induced with halothane, oxygen, and nitrous oxide 4–5% (FIO2 50%) administered via a snout mask. After tracheal intubation halothane was reduced to 1–2% and mechanical ventilation established with a volume-cycled ventilator (Blease-Brompton-Manley, Chesham, Bucks, UK) (tidal volume 10–15 ml kg–1; rate 12–15 bpm). At the end of surgery, inspired halothane concentration was reduced to less than 0.25% and an i.v. infusion of alphaxalone-alphadolone (Saffan; Pitman-Moore, Uxbridge, UK; 15 mg kg–1 h–1) commenced. Inspired oxygen was also reduced to between 0.25 and 0.3.
Using aseptic techniques, the right external jugular vein was exposed and a pulmonary artery floatation catheter (Baxter Swan-Ganz CCO/VIP, 7.5F; Edwards Life Sciences, CA, USA) was introduced. Correct positioning of the pulmonary artery catheter was confirmed by inspecting the transduced waveforms. All animals received maintenance fluids (NaCl 0.9%; 10 ml kg–1 h–1) via the central vein to replace insensible fluid loss (this infusion was discontinued during the ‘shock procedure’ and restarted after resuscitation). The femoral artery was then exposed surgically and the dilution catheter (Pulsiocath PV 2024 4F; Pulsion Medizintechnik, Munich, Germany) was positioned in the abdominal aorta. An indwelling suprapubic Foley catheter was positioned for continuous drainage of urine. At the end of the instrumentation phase (considered time 0) all animals were given a rest period of 30 min following which baseline measurements were made. This was followed by the ‘shock procedure’ in Groups S and G. A captive bolt (Cox Universal model V/10165; Temple Cox Development, Bromley, Kent, UK) was used to achieve bilateral tibial fractures. The bolt was applied directly to the bone in order to minimize soft tissue damage. Haemorrhage was then commenced at a rate of 1 ml kg–1 min–1 and continued until three of the four predetermined end points of shock were achieved. Shock was achieved in all animals within 30 min and the end points for shock were as follows.
1. Greater than 30% reduction in CO.
2. Greater than 30% reduction in mean arterial pressure (MAP).
3. Mixed venous oxygen saturation (SvO2) less than 40%.
4. Blood lactate concentration greater than 3 mmol litre–1.
Shock was maintained for 1 h (shock phase) and further blood was removed as necessary during this phase in order to ensure at least three ‘shock criteria’ were maintained throughout this period. ‘Start of shock phase’ measurements and ‘end of shock phase’ measurements were made at the beginning and end of the shock phase, respectively. At the end of the shock phase, volume resuscitation was achieved with either NaCl 0.9% (S group) or gelatine (G group). Fluid administration was stopped when CO was restored and maintained above 90% of baseline values throughout the resuscitation phase (60 min) followed by the post-resuscitation phase measurements. The animals were killed by anaesthetic overdose, chest opened, lungs removed, and EVLW content was determined by a gravimetric method, which corrects for intravascular volume.16
Measurement of extravascular lung water index
The dual dye dilution method (COLD Z-03; Pulsion Medizintechnik, Munich, Germany) was used to estimate extra vascular lung water index (EVLWi) at the following time points.
1. Baseline: 30 min after completion of the instrumentation phase.
2. Start of shock phase: 60 min after completion of the instrumentation phase.
3. End of shock phase: 120 min after completion of the instrumentation phase.
4. Post-resuscitation phase: 180 min after completion of the instrumentation phase.
Triplicate estimates of EVLWi using a manual injection of 10 ml of cold indocyanin green (Pulsion; 1 mg ml–1) were made and the numerical average of the two closest measurements was taken as the true EVLWi for each phase. Dynamic lung compliance (Cdyn), PaO2/FIO2 ratio, venous admixture (Q·S/Q·T), mean pulmonary arterial pressure (MPAP), MAP, CO, arterial blood lactate concentration were also measured at the same time points as EVLWi in all three groups. A stopwatch was used in all experiments in order to make the respective measurements at the same time points in the three groups.
Measurement of dynamic lung compliance (Cdyn)
A tracheal tube with a purpose-built pressure monitoring port was used to intubate the trachea (Mallinkrodt, Hi-Lo Jet; size 6.5). An oesophageal balloon (Mallinkrodt, size 8.5) was positioned in the mid-oesophagus and the pressure monitoring ports of both tubes were connected to a differential pressure transducer (Pneu-01; World Precision Instruments, Inc., USA) to obtain transpulmonary pressure signals. A Pneumotachograph (Godart 17212; Gould Electronics BV, The Netherlands) was used for respiratory flow measurements. Transpulmonary pressure and respiratory flow signals were acquired and stored in a personal computer using standard equipment and software (CED 1902, CED 1401 and Spike 2; Cambridge Electronics Design, Cambridge, UK). Tidal volume was obtained by integrating the inspiratory flow signals and Cdyn was calculated17 for baseline, end of shock, and post-resuscitation phases.
Measurement of pulmonary venous admixture (Q·S/Q·T) and blood lactate concentrations
Arterial and mixed venous blood samples were obtained simultaneously during the four phases of measurement. Mixed venous blood was sampled using a low pressure aspiration technique to prevent contamination with left atrial blood18 and the samples were analysed immediately in the blood gas analyser/oximeter (ABL 330/OSM3; Radio meter, Copenhagen, Sweden) and lactate analysers (BEG 2300; YSI Ltd, UK).
CO and systemic/pulmonary vascular resistance
Using the Vigilance continuous CO monitor (Baxter Healthcare Ltd, CA, USA) continuous cardiac output (CCO) and intermittent thermodilution CO were determined. CO data used in all subsequent analyses are based on values obtained using the intermittent technique. The CCO measurements were used to identify the end points of shock and adequacy of fluid resuscitation only. Pulmonary vascular resistance (PVR) was derived from MPAP, pulmonary capillary wedge pressure (PCWP) and CO in the customary fashion: PVR=[(MPAP – PCWP)/CO]*80. As right atrial pressure measurements were not made (because of technical difficulties inherent in placing an additional catheter in the right atrium) a proxy measure of systemic vascular resistance (SVR’) was derived in the following way: SVR’=MAP/CO*80.
Statistical analyses
All variables were analysed using analysis of variance (ANOVA) for repeated measurements (general linear model; SPSS 9.0, SPSS, Inc., Chicago, IL, USA). Change in PVR during the course of the experiment (PVRpost-resuscitation–PVRbaseline) was compared between the groups using one-way ANOVA. When using the repeated measures ANOVA, significant factors were further compared using 95% CI of the estimated means at each of the four phases of the experiment. Statistical significance was defined as P<0.05 (two-tailed). As all data were normally distributed mean (SD) and corresponding ranges have been used as summary statistics.
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Results |
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The mean (SD) weights for the three groups were comparable (C, 26.8 kg (3.0); S, 27.5 kg (2.5); G, 27.8 kg (3.8)). Two animals died during the experiments, one each from ‘S’ and ‘G’ groups. As both animals died during the latter stages of the resuscitation phase all available measurements from both animals have been included in the subsequent analyses. Mean (SD) values for the four parameters used in the definition of shock, i.e. CO, MAP, SvO2, and blood lactate concentration are summarized in Table 1. All other measured and derived variables, i.e. PCWP, heart rate (HR), stroke volume (SV), left ventricular stroke work (LVSW), MPAP, MPAP/MAP ratio, PVR, SVR’, EVLWi, PaO2/FIO2, Q·S/Q·T, and Cdyn are shown in Table 2. There were no significant differences in any of the baseline parameters (Tables 1 and 2).
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As expected from the study design there was a significant reduction in CO, MAP, and SvO2 associated with the ‘shock procedure’ (Table 1). As a rise in blood lactate concentration is a relatively delayed event, all four ‘shock criteria’ (including blood lactate concentration >3 mmol litre–1) were achieved during the shock phase in only 12 animals. The percentage blood volume removed from the two groups of animals as comparable (S=39.4% (6.7); range 25–50%; G=39.1% (11.6); range 24–60%). As expected the volume of saline infused to achieve the resuscitation targets was greater than the volume of colloids (803 ml (258); range 402–1275 ml compared with 699 ml (274); range 438–1300 ml). This difference, however, did not reach statistical significance. Volume replacement restored CO to control values in both shock groups. In spite of this, MAP remained significantly below control values in both groups (95% CI: C=70–95, S=28–52, G=45–69 mm Hg). The low MAP in the presence of a normal CO was associated with a significant reduction in SVR’ in both shock groups at the end of the resuscitation phase (95%CI: C=1613–2264, S=664–1315, G=853–1505 dynes s cm–5). A small but non-significant increase in MPAP was observed for the two shock groups during the study period. However, the ratio MPAP/MAP was significantly greater in the two shock groups at the end of resuscitation (95% CI: C=0.12–0.30; S=0.43–0.61; G=0.32–0.49). The higher MPAP/MAP ratio was associated with a significant increase in PVR in Group S during the study period (F=3.9; P<0.05). Even though the mean change in PVR for Group G was greater than the control group this difference was not statistically significant (C: mean change=–29; 95% CI=–132–77 dynes s cm–5; G: mean change=56; 95% CI=–91–204 dynes s cm–5).
Mean SV at the post-resuscitation phase was substantially less in Group S than in Groups C and G even though this difference did not reach statistical significance (95% CI: C=23.5–33.9, S=16.6–27, G=23.1–33.5 ml). When compared with baseline values, however, both shock groups showed a significant reduction (LVSWpost-resuscitation– LVSWbaseline) in LVSW (F=19.4, P<0.001) closely following the observed trends in MAP. Mean SvO2 recovered to above 40% after resuscitation but remained significantly below control in both shock groups, reflecting haemodilution and a reduction in oxygen delivery consequent on the asanguineous fluids used.
Blood lactate concentration continued to rise after resuscitation in Groups S and G. Post-hoc analysis, however, showed that this apparent worsening of shock occurred only in those animals that met all four ‘shock criteria’ (n=12) before the end of the shock phase (Fig. 1). In order to explain the underlying reasons for persistent hyper lactataemia in these animals further post-hoc comparisons between oxygen delivery (DO2), oxygen consumption (VO2) and arterial-mixed venous oxygen content difference [C(a–v)O2] was made between three post-hoc groups [C: control group (n=9); B: group of animals that did not meet the ‘lactate criteria’ during the shock phase (n=8) and A: group that met the ‘lactate criteria’ during the shock phase (n=12)]. The results are summarized in Table 3. In both shock groups the mean DO2 following volume replacement was less than the control groups with a greater and statistically significant reduction in Group A (95% CI: C=313–443, B=215–346, A=176–298 ml min–1). This reduction in DO2 was, however, not accompanied by a corresponding increase in C(a–v)O2 in either shock group. (95% CI for C(a–v)O2 at the post-resuscitation phase: C=35–50, B=27–41, and A=35–47 ml litre–1). There was no significant difference in the volume of blood loss between groups that met all four ‘shock criteria’ and those that met only three of the four criteria (41% (9); range 25–60 vs 36% (8); range 24–50% of total blood volume).
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Overall, there were no significant changes in PaO2/FIO2, Q·S/Q·T, EVLW, or Cdyn during the experiments (Table 2). However, in five experiments a greater than 30% increase in EVLWi was observed during the period of study. Four of these animals showed an increase in blood lactate greater than 3 mmol litre–1 during the shock phase (S=3, G=1). A greater than 10% reduction in lung compliance was seen in four experiments (one in C and three from S and G). Both animals that died showed blood lactate concentration greater than 3 mol litre–1 during the shock phase (with further rise in blood lactate concentration during the resuscitation phase), greater than 30% increase in EVLWi and greater than 10% reduction in Cdyn.
A comparison between the COLD system and gravimetric methods showed that the former method consistently underestimated EVLWi (Bland-Altman plot: bias=64 ml; SD=44 ml). At post-mortem examination it was observed that three animals (S=2; G=1) had increased amounts of fluid within the pleural and pericardial spaces. All three showed a greater than 30% increase in EVLWi and two died during resuscitation.
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Discussion |
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Acute lung injury is generally recognized as a late complication and few studies in the literature have explored its importance in the initial clinical presentation of shock.3–5 The current study reproduces the physiological findings occurring in patients with a combination of moderate skeletal trauma and acute haemorrhage and investigates the pulmonary changes within the first hour after the onset of shock. Overall, no significant changes in oxygenation, compliance, or EVLWi were demonstrable either at the end of the shock period or after initial fluid resuscitation. A significant increase in relative pulmonary pressures and PVR, however, was evident even within this relatively short time period. Relative pulmonary hypertension was demonstrable in both groups at the end of the shock phase (95% CI for MPAP/MAP ratio at the end of shock phase; C=0.15–0.24, S=0.28–0.38, G=0.32–0.42) and persisted even after volume replacement with either crystalloid or colloid solutions.
Post-traumatic shock has three important facets: hypovolaemia, pain, and tissue injury and it is recognized that haemodynamic responses to haemorrhage are altered significantly by concomitant nociception and injury.19 20 As both local and systemic factors are important in the evolution of lung injury bilateral long bone fractures and haemorrhage were included in the present model. The end points of shock in most published laboratory work have been based on removal of a predetermined percentage of blood volume,19 20 removal of blood until a predetermined arterial blood pressure was achieved21 or alterations in resting membrane potential (RMP).3 Clinical evaluation of shock, however, is based on the extent of global blood flow reduction and the consequences of tissue ischaemia. To the best of our knowledge this is the first study that took a combination of blood flow-based measurements (CO) and clinical measures of tissue ischaemia (SvO2 and blood lactate concentration) in the definition of shock in laboratory models. The threshold value for blood lactate concentration was 3 mmol litre–1 as patients with blood lactate concentration greater than 3 mmol litre–1 on admission to an emergency department are known to carry a worse prognosis than others.22 In the UK, victims of major trauma and shock receive fluid resuscitation at the site of injury by trained paramedical staff as an immediate priority. As a result, untreated shock lasting for more than an hour is rare and the shock phase in the present study was restricted to one hour in keeping with this clinical reality.
The choice of anaesthetic agent is always difficult, as all agents will modify the cardiovascular responses to trauma and shock to some extent. ‘Saffan’ was chosen for most part of the study as it is the only agent that has been shown to preserve the cardiovascular responses to trauma.23 Halothane was used at the beginning to facilitate intubation without neuromuscular blocking agents and a predominantly ‘Saffan’ based anaesthetic regimen was used as soon as vascular access was established. Some important limitations of the study, however, require emphasis. Most importantly, volume replacement was stopped when CO was restored and maintained to within 90% of baseline as it was essential to limit the volume of clear fluid administered to prevent unacceptable levels of haemodilution and premature death. Both shock groups were therefore under-resuscitated by design. A low MAP associated with inadequate volume resuscitation and a ‘normal’ MPAP associated with hypoxic pulmonary vasoconstriction (as a result of low SvO2)24 may also account for the observed changes in MPAP/MAP and PVR. Adequate resuscitation after major haemorrhage requiring blood transfusion and volume replacement with clear fluids always raises the question of volume overload (absolute or relative to a constricted circulation) in relatively short experimental studies such as ours. As the primary hypothesis was that shock per se results in increased EVLW, under resuscitation would not have been important had we demonstrated a significant increase in EVLWi. As an increase in EVLWi was not demonstrated and the conclusions are based on changes to pulmonary and systemic arterial pressures, adequacy of volume resuscitation is an important confounding factor. In this context some of the incidental findings reported in a more recent study are extremely pertinent and should be considered along with our findings. In a similar study by Chiara and colleagues,21 (with a shock period of 1 h followed by fluid/blood resuscitation over 2 h) in spite of adequate resuscitation (including restoration of haemoglobin and MAP) MPAP, the ratio MPAP/MAP and PVR remained significantly higher than the corresponding baseline values. As the study was not designed to evaluate the pulmonary consequences of shock the above authors did not explore these incidental findings further or comment upon their significance. The significant reduction in SVR’ in the present study (at the post-resuscitation phase) suggests that sympathetically mediated vasoconstriction was overcome by the effects of reperfusion. Further, in the two animals that died relative pulmonary hypertension was associated with a large increase in EVLW (>30%), reduction in Cdyn, and increased fluid within the pleural and pericardial spaces. These additional features and the data reported by Chiara and colleagues21 support our conclusion that pulmonary vascular changes may begin within the first hour after the onset of shock. This observation, if confirmed by further clinical studies is very relevant to the management of patients with prolonged shock.
Many of the derived haemodynamic parameters (SV, LVSW, SVR’, and PVR) are invariably linked to changes in CO, HR, MAP, and MPAP. Nevertheless, such derived parameters remain popular and useful in the critical care setting and, therefore, we have applied them to the present study. Right atrial pressure measurements were not made and, therefore, a surrogate measure of SVR’ has been used to assess the systemic vascular bed. Inclusion of right atrial pressure in the derivation of SVR is likely to amplify the observed differences in SVR’ even further (because of the lower MAP in the two shock groups) and this makes the reported differences relevant. The derivation of SVR’ during the shock phase (or PVR for that matter) is based on the assumptions that blood flow through a constricted circulation is laminar and blood is a Newtonian fluid.25 Both assumptions are invalid in the presence of profound vasoconstriction and hypovolaemia and this is a recognized limitation of calculated vascular resistance. Therefore, all comments on SVR’ and PVR are based on measurements made at baseline and during the post-resuscitation phase only. Thirdly, the duration of the instrumentation phase varied during the period of study as a result of the learning curve inherent in undertaking surgical instrumentation. This effect, however, was taken into account in the experimental design by adhering to a strict randomization protocol.
Early changes in lung function has been reported previously in pigs by Noble4 and in baboons by Holcroft and colleagues.3 The lack of a control group in Noble’s study design renders the findings inconclusive and the clinical significance of shock defined by RMP criteria by Holcroft and colleagues is unclear. We have, therefore, used more clinically relevant criteria such as CO, MAP, blood lactate concentration, and SvO2. The study shows that in the early stages of shock commonly monitored parameters such as PaO2/FIO2, Q·S/Q·T, Cdyn, and EVLWi may remain unaltered (except in the more severe and irreversible forms of shock). Changes in relative pulmonary pressures (MPAP/MAP) may in fact be the earliest evidence of pulmonary vascular changes in such patients. The present study clearly highlights the differences between pulmonary and systemic vascular beds to ischaemic reperfusion. Translocation of gut-derived endotoxins into the systemic circulation following mesenteric ischaemia is a well-recognized cause for intense pulmonary vasoconstriction associated with systemic vasodilatation.6 26 We believe this is one of the possible explanations for the differences in the systemic and pulmonary circulations seen after volume replacement in the present study.
The reasons for a persistent elevation in blood lactate concentration in some animals even after fluid resuscitation is complex. Post-hoc analysis shows that even though fluid resuscitation resulted in improvements in DO2 post-resuscitation DO2 values were substantially below that of the control group and baseline values for each of the post-hoc groups. In spite of the low DO2 global oxygen extraction (reflected by C(a–v)O2) remained within normal limits. This implies that a combination of reduced oxygen delivery and defective extraction contributed to the persistent elevation in blood lactate concentration. In keeping with current clinical consensus14 15 no major differences were seen between the two groups resuscitated with either gelatine or saline. Both shock groups showed a significant reduction in mean SVR’ associated with an increase in mean PVR following volume resuscitation. The lack of a statistically significant rise in PVR for Group G we believe, is attributable to the relatively small numbers of animals in each group. The calculation of sample size, however, was based on the number of animals required within each group to demonstrate a more than 20% rise in EVLWi during the study period. Thus, even though the study was not specifically powered to demonstrate differences between the two fluid groups, differences if any are likely to be small and unimportant. The percentage blood volume removed from each group was similar (Group S=39.4% (SD=6.7%); Group G=39.1% (SD=11.6%)) although the amount of blood removed from individual animals ranged from 24–60% of total blood volume highlighting the limitations of many traditionally used shock models based on fixed percentage volume loss.19 20 The present finding is in keeping with the clinical observation that the haemodynamic and metabolic consequences of haemorrhage and shock vary markedly in healthy subjects.
In conclusion, the present study suggests that pulmonary and systemic vascular dysfunction may be demonstrable within the first hour after the onset of shock. As such the stage for subsequent development of acute lung injury and or multiple organ failure may be set very early in the clinical course of shock and should be an important consideration in the initial resuscitation of patients presenting with shock. As a result of ethical and financial constraints it was not possible to include larger numbers of animals in the present study and therefore further laboratory studies where DO2 and SvO2 values are restored and maintained over a longer period are necessary to confirm the above findings and to elucidate the pathophysiology of early pulmonary changes in shock.
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Acknowledgements |
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We are grateful to Dr M. O. Columb, South Manchester University Hospitals for the assistance in data analysis. The role of Mrs H. Marshall and Mr T. Riney in conducting these experiments is gratefully acknowledged. The studies were funded by the Medical Research Council UK and Maelor Pharmaceuticals, Wrexham (UK). Data included in this paper were presented to the Anaesthetic Research Society, UK in March 2001.
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References |
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