Emrys Kirkman

Physiologic responses to primary blast.

BACKGROUND Primary blast injuries are produced by the blast shock wave. The critical determinant of survival is pulmonary injury, but acute cardiorespiratory responses to blast exposure are not well understood. The aim of this study was to investigate these changes. METHODS Twenty anesthetized rats were exposed to moderate blast overpressure, 10 animals receiving thoracic and 10 receiving abdominal exposure. Another 9 animals acted as controls. Respiration, heart rate, and blood pressure were recorded continuously before, during, and for 6 hours after blast exposure. RESULTS All animals exposed to thoracic blast demonstrated apnea, bradycardia, and hypotension after blast exposure, followed by a return to preblast values. No significant cardiovascular or respiratory changes were seen in animals in the other groups. CONCLUSION Moderate thoracic blast injury produces a reflex triad of apnea, bradycardia, and hypotension that is not present after abdominal blast. These observations may have important implications for the immediate management of patients with blast injuries.

Prolonged permissive hypotensive resuscitation is associated with poor outcome in primary blast injury with controlled hemorrhage.

Objective:To determine the effects of primary blast injury (PBI) on survival and the physiological response to resuscitation after hemorrhagic shock. Background:Air-blast injury is a significant clinical problem that can reduce blood oxygenation and modify the response to hemorrhage. PBI has specific physiological effects that have not been fully accounted for in resuscitation strategies. Permissive hypotension is a widely adopted strategy in trauma resuscitation. However, the choice of resuscitation strategy requires a full understanding of the mechanisms of injury and their physiological consequences. Methods:Terminally anesthetized pigs were divided into 4 groups and subjected to either air-blast injury (B) or no blast (S). All received a controlled hemorrhage of 30% blood volume and resuscitation with 0.9% saline to a normotensive (Normot, systolic blood pressure 110 mm Hg) or hypotensive (Hypot, 80 mm Hg) end point for up to 8 hours. (n = 6 in each B and n = 8 in each S subgroup). Results:Survival time was significantly shorter with Hypot (P < 0.0001 Peto log rank). The effect was in the animals subjected to B (P = 0.0005) (mean survival time [95% CI]; BNormot 422 [313–531] vs. BHypot137 [94–181] min), but not those given S (P = 0.06) (SNormot 480 [all survived] vs. SHypot 352 [210–494] min). PBI exacerbated a profound metabolic acidosis during Hypot, possibly due to an overwhelming compromise in tissue oxygen delivery. Conclusions:Prolonged hypotensive resuscitation is not compatible with survival after primary blast. Casualties most likely to be in this category are those injured by blast in confined spaces or by enhanced blast weapons. The risk of rebleeding associated with normotensive resuscitation needs to be balanced with the metabolic derangement associated with hypotensive resuscitation.

Reflex nature of the cardiorespiratory response to primary thoracic blast injury in the anaesthetised rat.

Blast injuries represent a problem for civilian and military populations. Primary thoracic blast injury causes a triad of bradycardia, hypotension and apnoea. The objective of this study was to investigate the reflex nature of this response and its modulation by vagotomy or administration of atropine. The study was conducted on terminally anaesthetised (alphadolone/alphaxalone, 18‐24 mg kg h−1, I.V.) male Wistar rats randomly allocated to the groups indicated below. Blast injuries were produced with compressed air while sham blast involved the sound of a blast only. Primary blast injury to the thorax resulted in a bradycardia (measured as an increase in the interval between beats, or heart period (HP) to 489 ± 37 ms from 133 ± 3 ms with a latency of onset of 4.3 ± 0.3 s, mean ± S.E.M.), hypotension (fall in mean arterial blood pressure (MBP) from 128.1 ± 3.7 mmHg to 34.8 ± 4.1 mmHg, latency of onset 2.0 ± 0.1 s) and apnoea lasting 28.3 ± 2.3 s. Sham blast had no effect. The bradycardia and apnoea following thoracic blast were abolished by cervical vagotomy while the hypotension was attenuated. Atropine (0.3 mg kg−1, I.V.) caused a significant reduction in the bradycardia (HP increasing from 124 ± 3 ms to 142 ± 4 ms) but did not modulate either the hypotension or apnoea. It is concluded that a reflex involving the vagus nerve mediates the bradycardia, apnoea and a component of the hypotension associated with thoracic blast. The pattern of this response is similar to effects that follow stimulation of the pulmonary afferent C‐fibres.

Targeted resuscitation improves coagulation and outcome.

BACKGROUND: Acute trauma coagulopathy in seriously injured casualties may be initiated by tissue hypoperfusion. A targeted (or novel hybrid [NH]) resuscitation strategy was developed to overcome poor tissue oxygen delivery associated with prolonged hypotension. METHODS: Under the Animals (Scientific Procedures) Act 1986, terminally anesthetized large white pigs were divided into four groups (n = 6). Groups 1 and 2 received blast injury and 3 and 4 no blast (sham). All were given a controlled hemorrhage (35% blood volume) and an uncompressed grade IV liver injury. Five minutes later, all were resuscitated with 0.9% saline to a systolic arterial pressure (SAP) of 80 mm Hg. After 60 minutes, the NH groups (1 and 3) were resuscitated to a SAP (110 mm Hg), whereas hypotensive groups (2 and 4) continued with SAP 80 mm Hg for up to 8 hours from onset of resuscitation. RESULTS: Mean survival time was shorter in group 2 (258 minutes) compared with groups 1, 3, and 4 (452 minutes, 448 minutes, and 369 minutes). By the end of the study, hypotension was associated with a significantly greater prothrombin time (1.73 ± 0.10 and 1.87 ± 0.15 times presurgery, groups 2 and 4) compared with NH (1.44 ± 0.09 and 1.36 ± 0.06, groups 1 and 3, p = 0.001). Blast versus sham had no significant effect on prothrombin time (p = 0.56). Peak levels of interleukin 6 were significantly lower in NH groups. Arterial base excess was significantly lower with hypotension (−18.4 mmol/L ± 2.7 mmol/L and −12.1 mmol/L ± 3.2 mmol/L) versus NH (−3.7 mmol/L ± 2.8 mmol/L and −1.8 mmol/L ± 1.8 mmol/L, p = 0.0001). Hematocrit was not significantly different between groups (p = 0.16). CONCLUSION: Targeted resuscitation (NH) attenuates the development of acute trauma coagulopathy and systemic inflammation with improved tissue perfusion and reduced metabolic acidosis in a model of complex injury. This emphasizes the challenge of choosing a resuscitation strategy for trauma patients where the needs of tissue perfusion must be balanced against the risk of rebleeding during resuscitation.

A comparison of the effects of skeletal muscle injury and somatic afferent nerve stimulation on the response to hemorrhage in anesthetized pigs

The effect of skeletal muscle injury (SMI) on cardiovascular and O2 transport responses to hemorrhage (HS) were examined in anesthetized pigs. Bilateral hindlimb muscle was injured 75 minutes before HS was started at a rate of 0.75 mL/min.kg until a total of 30 mL/kg (40% estimated total blood volume) had been removed. The reductions in cardiac index (CI), left ventricular stroke work, and oxygen delivery (Do2) and the increase in plasma lactate concentration following HS were exacerbated by SMI such that although oxygen consumption was maintained after HS it fell after SMI + HS. The deleterious effect of SMI on the response to HS was greater than that recorded previously following somatic brachial nerve stimulation (BNS). Thus, in order to achieve a given reduction in CI and Do2 or a rise in Shock Index (heart rate divided by systolic blood pressure) to approximately 3, a blood loss of 40% was needed after HS; this was reduced to 36% by the addition of BNS, whereas a loss of only 29% was needed when SMI was introduced. The mechanism of the deleterious effect of SMI is unclear although a change in the distribution of regional blood flow and a rise in the critical oxygen delivery may be implicated.

Use of stroke distance in the early detection of simulated blood loss

OBJECTIVES To compare the effects of simulated and mild actual hemorrhage on parameters used traditionally to assess hemorrhaging patients: heart rate (HR), blood pressure (BP), and Shock Index (SI = HR/systolic BP), with stroke distance (SD) measured ultrasonically as an index of cardiac stroke volume. MATERIALS AND METHODS Hemorrhage was simulated in 19 healthy volunteers by the application of graded lower-body negative pressure (LBNP) (0, -20, -40, and -60 mm Hg) to pool blood in the lower body and reduce venous return. Measurements were also made before and after a standard blood donation (450 mL) in nine healthy volunteers. MEASUREMENTS AND MAIN RESULTS SD decreased significantly and progressively from the baseline level of 23.8+/-5.7 cm (mean+/-SD) at each level of LBNP: by 3.4+/-1.9, 7.4+/-2.5, and 11.8+/-3.2 cm at LBNP of -20, -40, and -60 mm Hg, respectively. Neither HR nor SI changed significantly at the lowest level of LBNP (-20 mm Hg), but they showed progressive, significant increases thereafter. Mean BP did not change significantly at any level of LBNP. Similarly, after a controlled hemorrhage of 450 mL, SD decreased significantly by 3.3+/-1.6 cm from 22.2+/-2.8 cm, whereas HR and SI remained unchanged and mean BP increased slightly. CONCLUSION Changes in SD may provide an earlier indication of progressive blood loss than either HR or BP alone or in combination.

Cardiovascular response to graded lower body negative pressure in young and elderly man

Lower body negative pressure (LBNP) reduces central venous pressure (CVP) and cardiac output. The elderly are reported to have a limited capacity to increase cardiac output by increasing heart rate (HR), are especially dependent on end diastolic volume to maintain stroke volume and therefore should be especially vulnerable to LBNP. The present study compared the effects of LBNP in the young and old. Stroke volume was assessed non‐invasively as stroke distance (SD) by aortovelography. Two groups of healthy male volunteers were studied: eight young (29.7 ± 2.0 years, mean ± S.E.M.) and nine old (70.1 ± 0.9 years). LBNP was applied progressively at 17.5, 35 and 50 mmHg in 20 min steps, with measurements taken during each steady state. There were similar, significant, falls in CVP in both groups. SD fell significantly in both groups from respective control values of 24.8 ± 1.6 and 16.6 ± 0.9 cm to 12.5 ± 1.3 and 8.9 ± 0.4 cm at a LBNP of 50 mmHg. Although SD in the elderly was significantly lower than in the young, the LBNP‐induced changes were not different between groups. Both groups produced similar significant increases in vascular resistance, HR, plasma vasopressin (AVP) and noradrenaline. Mean arterial blood pressure (MBP) and plasma adrenaline did not change significantly. Therefore healthy old men respond to LBNP in a similar manner to the young, although MBP and SD are regulated around different baselines in the two groups.

The effect of nociceptive stimulation on the changes in hemodynamics and oxygen transport induced by hemorrhage in anesthetized pigs.

The effects of somatic nociceptive afferent stimulation on aspects of cardiac function and oxygen transport were examined in a model of hemorrhage in anesthetized pigs. The brachial nerves were stimulated (BNS) alternately to obtain a rise in heart rate of 18% and in mean arterial pressure of 17%. This stimulation was started 75 minutes before the start of hemorrhage and maintained throughout and after the withdrawal of blood. The animals were bled at a rate of 0.75 ml/min.kg until a total of 30 ml/kg had been removed. At the end of hemorrhage the reductions in cardiac index (CI), stroke volume (SV), and left ventricular stroke work (LVSW) were greater in the BNS group compared with controls. The nociceptive stimulation also elicited greater reductions in oxygen delivery (DO2I) and oxygen consumption (VO2) and a greater rise in the arterial plasma lactate concentration. Thus it seems that nociceptive stimulation exacerbates the changes in systemic oxygen transport and cardiac function induced by hemorrhage.

Evaluation of Prehospital Blood Products to Attenuate Acute Coagulopathy of Trauma in a Model of Severe Injury and Shock in Anesthetized Pigs

ABSTRACT Acute trauma coagulopathy (ATC) is seen in 30% to 40% of severely injured casualties. Early use of blood products attenuates ATC, but the timing for optimal effect is unknown. Emergent clinical practice has started prehospital deployment of blood products (combined packed red blood cells and fresh frozen plasma [PRBCs:FFP], and alternatively PRBCs alone), but this is associated with significant logistical burden and some clinical risk. It is therefore imperative to establish whether prehospital use of blood products is likely to confer benefit. This study compared the potential impact of prehospital resuscitation with (PRBCs:FFP 1:1 ratio) versus PRBCs alone versus 0.9% saline (standard of care) in a model of severe injury. Twenty-four terminally anesthetised Large White pigs received controlled soft tissue injury and controlled hemorrhage (35% blood volume) followed by a 30-min shock phase. The animals were allocated randomly to one of three treatment groups during a 60-min prehospital evacuation phase: hypotensive resuscitation (target systolic arterial pressure 80 mmHg) using either 0.9% saline (group 1, n = 9), PRBCs:FFP (group 2, n = 9), or PRBCs alone (group 3, n = 6). Following this phase, an in-hospital phase involving resuscitation to a normotensive target (110 mmHg systolic arterial blood pressure) using PRBCs:FFP was performed in all groups. There was no mortality in any group. A coagulopathy developed in group 1 (significant increase in clot initiation and dynamics shown by TEG [thromboelastography] R and K times) that persisted for 60 to 90 min into the in-hospital phase. The coagulopathy was significantly attenuated in groups 2 and 3 (P = 0.025 R time and P = 0.035 K time), which were not significantly different from each other. Finally, the volumes of resuscitation fluid required was significantly greater in group 1 compared with groups 2 and 3 (P = 0.0067) (2.8 ± 0.3 vs. 1.9 ± 0.2 and 1.8 ± 0.3 L, respectively). This difference was principally due to a greater volume of saline used in group 1 (P = 0.001). Prehospital PRBCs:FFP or PRBCs alone may therefore attenuate ATC. Furthermore, the amount of crystalloid may be reduced with potential benefit of reducing the extravasation effect and later tissue edema.

The Effects of Primary Thoracic Blast Injury and Morphine on the Response to Haemorrhage in the Anaesthetised Rat

Primary thoracic blast injury causes a triad of bradycardia, hypotension and apnoea mediated in part via a vagal reflex. Blast casualties may also suffer blood loss, and the response to progressive simple haemorrhage is biphasic: an initial tachycardia followed by a vagally mediated reflex bradycardia which can be attenuated by μ opioid agonists. The aims of this study were to determine the effects of thoracic blast injury on the response to subsequent haemorrhage, and the effects of morphine, administered after blast, on the response to blood loss. Male Wistar rats, terminally anaesthetised with alphadolone‐alphaxolone (19‐21 mg kg−1 h−1 I.V.), were allocated randomly to one of three groups: Group I, sham blast; Group II, thoracic blast; Group III, thoracic blast plus morphine (0.5 mg kg−1 I.V. given 5 min after blast). Blast (Groups II and III) resulted in significant (P < 0.05, ANOVA) bradycardia, hypotension and apnoea. Sham blast (Group I) had no effect. Ten minutes later, haemorrhage (40% of the estimated total blood volume (BV)) in Group I produced a biphasic response comprising a tachycardia followed by a peak bradycardia after the loss of 33% BV. Arterial blood pressure did not fall significantly until the loss of 13.3% BV. In Group II the haemorrhage‐induced tachycardia was absent and the bradycardia was augmented: peak bradycardia was seen after the loss of 23% BV. Mean arterial blood pressure (MBP) began to fall as soon as haemorrhage commenced and was significant after the loss of 10% BV. Morphine (Group III) prevented the haemorrhage‐induced bradycardia and delayed the significant fall in MBP until the loss of 30% BV. It is concluded that the response to thoracic blast injury augments the depressor response to haemorrhage while morphine attenuates this response.