Spectrum of coagulation profiles in severely injured patients - a subgroup analysis from the fluids in resuscitation of severe trauma trial.

BACKGROUND: Trauma-induced coagulopathy (TIC) is a major contributing factor to worsening bleeding in trauma patients. The objective of this study is to describe the spectrum of coagulation profiles amongst severely injured patients. METHODS: This is a retrospective study of all patients with complete baseline TEG coagulation parameters collected prior to randomisation in the FIRST (fluids in resuscitation of severe trauma) trial between January 2007 and December 2009. Parameters recorded for this study included patient demographics, mechanism of injury, admission vital signs, lactate, base excess, coagulation studies prothrombin time (PT), international normalised ratio (INR), thromboelastography (TEG) parameters, volume, and type of fluids administered, volume of blood products administered, length of intensive care unit (ICU) stay and major outcomes. RESULTS: A total of 87 patients were included in this study, with a median injury severity score (ISS) of 20 and 57.5 had a penetrating injury mechanism. Coagulopathy was highly prevalent in this cohort, of which a majority (69%) was diagnosed with hypercoagulopathy and 24% had a hypocoagulopathy status on admission. There was no difference in age, gender and amount of pre-hospital fluids administered across the three groups. The median volume of blood products was higher in the hypocoagulopathy group, although not statistically significant. Overall, the 30-day mortality rate was 13%, with case fatalities occurring in only coagulopathic patients: hypercoagulopathy (15%) and hypocoagulopathy (10%). CONCLUSION: TIC is not an infrequent diagnosis in severely injured patients resulting in increased morbidity and mortality. Determining the coagulation profile using TEG at presentation in this group of patients may inform appropriate management guidelines in order to improve outcome.

The anion study: effect of different crystalloid solutions on acid base balance, physiology, and survival in a rodent model of acute isovolaemic haemodilution.

BACKGROUND: Commercially available crystalloid solutions used for volume replacement do not exactly match the balance of electrolytes found in plasma. Large volume administration may lead to electrolyte imbalance and potential harm. We hypothesised that haemodilution using solutions containing different anions would result in diverse biochemical effects, particularly on acid-base status, and different outcomes. METHODS: Anaesthetised, fluid-resuscitated, male Wistar rats underwent isovolaemic haemodilution by removal of 10% blood volume every 15 min, followed by replacement with one of three crystalloid solutions based on acetate, lactate, or chloride. Fluids were administered in a protocolised manner to achieve euvolaemia based on echocardiography-derived left ventrical volumetric measures. Removed blood was sampled for plasma ions, acid-base status, haemoglobin, and glucose. This cycle was repeated at 15-min intervals until death. The primary endpoint was change in plasma bicarbonate within each fluid group. Secondary endpoints included time to death and cardiac function. RESULTS: During haemodilution, chloride-treated rats showed significantly greater decreases in plasma bicarbonate and strong ion difference levels compared with acetate- and lactate-treated rats. Time to death, total volume of fluid administered: chloride group 56 (3) ml, lactate group 62 (3) ml, and acetate group 65 (3) ml; haemodynamic and tissue oxygenation changes were, however, similar between groups. CONCLUSIONS: With progressive haemodilution, resuscitation with a chloride-based solution induced more acidosis compared with lactate- and acetate-based solutions, but outcomes were similar. No short-term impact was seen from hyperchloraemia in this model.

Volume therapy in trauma and neurotrauma.

Volume therapy in trauma should be directed at the restitution of disordered physiology including volume replacement to re-establishment of tissue perfusion, correction of coagulation deficits and avoidance of fluid overload. Recent literature has emphasised the importance of damage control resuscitation, focussing on the restoration of normal coagulation through increased use of blood products including fresh frozen plasma, platelets and cryoprecipitate. However, once these targets have been met, and in patients not in need of damage control resuscitation, clear fluid volume replacement remains essential. Such volume therapy should include a balance of crystalloids and colloids. Pre-hospital resuscitation should be limited to that required to sustain a palpable radial artery and adequate mentation. Neurotrauma patients require special consideration in both pre-hospital and in-hospital management.

Resuscitation with hydroxyethyl starch improves renal function and lactate clearance in penetrating trauma in a randomized controlled study: the FIRST trial (Fluids in Resuscitation of Severe Trauma).

BACKGROUND: The role of fluids in trauma resuscitation is controversial. We compared resuscitation with 0.9% saline vs hydroxyethyl starch, HES 130/0.4, in severe trauma with respect to resuscitation, fluid volume, gastrointestinal recovery, renal function, and blood product requirements. METHODS: Randomized, controlled, double-blind study of severely injured patients requiring >3 litres of fluid resuscitation. Blunt and penetrating trauma were randomized separately. Patients were followed up for 30 days. RESULTS: A total of 115 patients were randomized; of which, 109 were studied. For patients with penetrating trauma (n=67), the mean (sd) fluid requirements were 5.1 (2.7) litres in the HES group and 7.4 (4.3) litres in the saline group (P<0.001). In blunt trauma (n=42), there was no difference in study fluid requirements, but the HES group required significantly more blood products [packed red blood cell volumes 2943 (1628) vs 1473 (1071) ml, P=0.005] and was more severely injured than the saline group (median injury severity score 29.5 vs 18; P=0.01). Haemodynamic data were similar, but, in the penetrating group, plasma lactate concentrations were lower over the first 4 h (P=0.029) and on day 1 with HES than with saline [2.1 (1.4) vs 3.2 (2.2) mmol litre⁻¹; P=0.017]. There was no difference between any groups in time to recovery of bowel function or mortality. In penetrating trauma, renal injury occurred more frequently in the saline group than the HES group (16% vs 0%; P=0.018). In penetrating trauma, maximum sequential organ function scores were lower with HES than with saline (median 2.4 vs 4.5, P=0.012). No differences were seen in safety measures in the blunt trauma patients. CONCLUSIONS: In penetrating trauma, HES provided significantly better lactate clearance and less renal injury than saline. No firm conclusions could be drawn for blunt trauma. STUDY REGISTRATION: ISRCTN 42061860.

The effect of low molecular weight heparin (enoxaparin) on enhanced coagulation induced by crystalloid haemodilution.

The purpose of this study was to establish whether a low molecular weight heparin (enoxaparin) attenuated or abolished the enhanced coagulation induced by crystalloid fluid therapy. Twenty young, healthy male volunteers were injected subcutaneously with either enoxaparin 40 mg or saline on two separate occasions one week apart, in a randomised, blinded study. Twelve hours later, a blood sample was taken for thrombelastography analysis and haematocrit. Saline 14 ml.kg⁻¹ was then infused over thirty minutes and thrombelastography and haematocrit measurements repeated. There was a significant post-dilutional difference in the alpha angle (p = 0.002) and k-time (p = 0.001) between the two groups. There was a trend towards reduced shortening of r-time in the enoxaparin group compared to the saline control (p = 0.18). The findings suggest that enoxaparin diminished acceleration of clot formation due to haemodilution.

Magnesium in obstetrics.

Magnesium is a critical physiological ion, and magnesium deficiency might contribute to the development of pre-eclampsia, to impaired neonatal development and to metabolic problems extending into adult life. Pharmacologically, magnesium is a calcium antagonist with substantial vasodilator properties but without myocardial depression. Cardiac output usually increases following magnesium administration, compensating for the vasodilatation and minimising hypotension. Neurologically, the inhibition of calcium channels and antagonism of the N-methyl-d-aspartic acid (NMDA) receptor raises the possibility of neuronal protection, and magnesium administration to women with premature labour may decrease the incidence of cerebral palsy. It is the first-line anticonvulsant for the management of pre-eclampsia and eclampsia, and it should be administered to all patients with severe pre-eclampsia or eclampsia. Magnesium is a moderate tocolytic but the evidence for its effectiveness remains disputed. The side effects of magnesium therapy are generally mild but the major hazard of magnesium therapy is neuromuscular weakness.

Drug administration errors: a prospective survey from three South African teaching hospitals.

This prospective study was undertaken to determine the incidence of drug administration errors by anaesthetists at three tertiary South African hospitals. Hospitals A and C treat adults predominantly, whereas Hospital B is a paediatric hospital. Anaesthetists completed an anonymous study form for every anaesthetic performed over a six-month period. They were asked to indicate whether or not an error or near-miss had occurred and if so, the details thereof. A total of 30,412 anaesthetics were administered during the study period. The response rate and combined incidence of errors and near-misses was as follows: Hospital A 48.8% (1:320), B 81.3% (1:252) and C 48.1% (1:250). The overall response rate was 53% and the combined incidence was 1:274. Neither the experience of the anaesthetist nor emergency surgery influenced whether an error occurred or not. Most errors occurred during the maintenance phase of anaesthesia. The most common errors were those of substitution. At the paediatric hospital, incorrect dose was as frequent an error as substitution. Of all errors, 36.9% were due to drug ampoule misidentification; of these the majority (64.4%) were due to similar looking ampoules. Another 21.3% were due to syringe identification errors. No major complication attributable to a drug administration error was reported. Despite an increasing awareness of the problem together with suggestions in the literature to reduce the incidence, drug administration errors remain fairly common in South Africa. Failure to institute suggested solutions will continue to compromise patient safety.

Emergency department procedural sedation practice in Cape Town, South Africa.

BACKGROUND: There are no general policies or protocols for procedural sedation in the emergency department and no literature on present practice in South Africa. AIMS: To investigate procedural sedation (PS) practice in adults in emergency departments (EDs) in Cape Town, South Africa. METHODS: A cross-sectional descriptive study was performed by interviewing all ED managers and ED doctors in Cape Town meeting the criteria (open 24 h a day, staffed by full-time doctors, seeing adult patients and doctors who practice primarily emergency medicine and have performed at least one PS in the last 3 months). RESULTS: Data were collected from 13 units (5 public, 8 private) and 76 clinicians (48 public, 28 private). PS facilities are generally good in the private sector, but poor in the public sector (lacking in equipment, staff and protocols). Monitoring of patients during PS is often substandard, with only two thirds of clinicians using a minimum of blood pressure and pulse oximetry monitors during PS. Commonly used drugs for PS included midazolam, morphine and propofol (91%, 80% and 28%, respectively). Propofol (use of which is increasing in the international ED) is more likely to be used by experienced clinicians and those in the private sector. Surprisingly, almost half of clinicians would like propofol used on themselves hypothetically, although the majority (62%) said they had no or limited knowledge of its use and were concerned with its safety. CONCLUSIONS: The private sector is generally better serviced for PS than the public sector. Most ED clinicians use morphine and midazolam for PS. However, there is widespread awareness of propofol as an alternative and probably superior PS drug. Recommendations for improving PS include development of general protocols for PS, training of doctors at all levels and optimization of ED facilities and staffing.

Drug administration errors by South African anaesthetists--a survey.

OBJECTIVES: To investigate the incidence, nature of and factors contributing towards wrong drug administrations by South African anaesthetists. DESIGN: A confidential, self-reporting survey was sent out to the 720 anaesthetists on the database of the South African Society of Anaesthesiologists. RESULTS: A total of 133 questionnaires were returned for analysis (18.5% response rate). Of the respondents, 125 (94%) admitted to having inadvertently administered a wrong drug. Thirty respondents (22.6%) said they had made errors on at least four occasions. A total of 303 specific wrong drug administrations were described. Nearly 50% involved muscle relaxants. A further 43 incidents (14%) involved the erroneous administration of vasoactive drugs. Five deaths and 3 nonfatal cardiac arrests were reported. In 9.9% of incidents the anaesthetic time was prolonged by more than 30 minutes. Contributory causes identified included syringe swaps (40%), misidentification of drugs (27.1%), fatigue (14.1%), distractions (4.7%), and mislabelling of syringes (4.7%). Only 19% of respondents regularly use colour-coded syringe labels complying with the national standard. CONCLUSIONS: Most anaesthetists experienced at least one drug error. The incidence of wrong drug administrations by South African anaesthetists appears to be similar to that in Australasia and Canada. The commonest error was a 'syringe swap' involving muscle relaxants. Most drug errors are inconsequential. An important minority of incidents result in severe morbidity or death. The study supports efforts to improve ampoule labelling, to encourage the use of syringe labels based on the international colour code and to develop a national reporting system for such incidents.

Just scratching the surface: varied coagulation effects of polymer containers on TEG variables.

BACKGROUND AND OBJECTIVE: Different types of polymer surfaces affect the activation of platelets and coagulation pathway containers depending on their surface qualities. Importantly, this could produce variability of coagulation results obtained with thrombelastographical analysis. We assessed the effects of blood storage on thrombelastograph, TEG, variables using polypropylene and polycarbonate containers. METHODS: An in vitro experiment was performed, with eight volunteers in each limb. Fresh whole blood was stored in polypropylene or polycarbonate tubes prior to TEGanalysis, to assess the role of these plastics in the TEG results obtained. RESULTS: The polycarbonate tubes displayed slower onset of coagulation and greater variability of data for all four basic TEG variables (r-time, k-time, alpha-angle and maximum amplitude, P < 0.05). Polycarbonate results fell outside manufacturer reference ranges. CONCLUSIONS: It is likely that this is due to the altered surface properties and charge effects of the containers affecting proteins and platelets differently. Caution should be used in choosing which containers are used for storage of fresh blood prior to coagulation assessment, as variable results will follow where different types of plastic containers are employed.

Plasma volume changes associated with two hydroxyethyl starch colloids following acute hypovolaemia in volunteers.

This randomised double blind prospective study compared the effective intravascular volume expansion and maintenance, with two types of starches following induced haemorrhagic hypovolaemia. Twenty healthy male volunteers aged between 18 and 65 year were bled 10% of their total blood volume in fully monitored conditions and under the supervision of a trained specialist doctor and research nurse. The lost blood volume was replaced using one of the starch solutions. Effective intravascular volume expansion was monitored hourly using the (51)Cr radio-labelled red blood cell dilution technique, we compared the effects of two hydroxyethyl starch colloid preparations, one a high molecular weight and the other a low molecular weight preparation, on the plasma volume changes over time. The large molecular weight starch (Hextend) provided a less well-sustained volume expansion effect than the smaller one (Voluven)

Crystalloid preload versus rapid crystalloid administration after induction of spinal anaesthesia (coload) for elective caesarean section.

Current methods of crystalloid preload administration prior to spinal anaesthesia for elective caesarean section are relatively ineffective in preventing hypotension. This study examined the relevance of the timing of the fluid administered. Fifty women were randomly allocated to receive either 20 ml x kg(-1) of crystalloid solution during 20 minutes prior to induction of spinal anaesthesia (preload), or an equivalent volume by rapid infusion immediately after induction (coload). Significantly more patients in the coload group did not require vasopressor therapy pre-delivery (P=0.047). The coload group required a lower median dose (P=0.03) and a lower median number (P=0.04) of ephedrine doses for the treatment of maternal hypotension pre-delivery. There was no between-group difference in either the total cumulative dose, or in the total number of doses of ephedrine. Neonatal outcomes among the two groups were similar. Rapid crystalloid administration after, rather than over 20 minutes before the induction of spinal anaesthesia for elective caesarean section, may be advantageous in terms of managing maternal blood pressure prior to delivery.

The effects of a one unit blood donation on auto-haemodilution and coagulation.

The effect of haemodilution on coagulation has been extensively investigated. We investigated auto-haemodilution following a 10% blood loss (480 ml) and its effect on coagulation. Ten healthy, unstarved volunteers were enrolled. One unit of blood was taken from each volunteer. Concurrently blood was taken from the opposite arm prior to and immediately after the blood donation, and at 1, 2, 4 and 6 hours. It was tested for thrombelastography, haematocrit and endorphins. There was a significant decrease in r-time from the control sample to the sample taken immediately post blood donation. This value returned to baseline at 1 hour post donation and did not change again. There were no other significant changes in thromboelastographic parameters. Fractional plasma noradrenaline changes were significantly raised at 1 hour post donation (P = 0.048), returning to baseline by 2 hours post donation. The haematocrit showed a rapid (approximately 4%) fall during donation followed by a slow, but progressive decrease over six hours, falling by a mean of 8.3% from pre-donation values. A state of relative hypercoagulability is found immediately after a rapid 10% loss in circulating blood volume. This may be related to the rapid immediate haemodilution. It is unlikely that the sympathetic response to blood loss plays a role. However, after the initial drop, slow restoration of circulating blood volume by autodilution takes six to eight hours, and is not associated with enhanced coagulation. Of interest is that a 10% blood loss in a healthy person does not require volume replacement.

Citrated blood does not reliably reflect fresh whole blood coagulability in trials of in vitro hemodilution.

IMPLICATIONS: Citration and storage of whole blood markedly alter the Thrombelastograph effects of hemodilution on coagulation. The results of hemodilution studies in which citrated blood has been used to study coagulation may not be reliable.