Anaesthesia, Pain, Intensive Care and Emergency - Part 10 pps

Propofol Propofol is a GABA-ergic alkyl phenol compound diluted in a long-chain triglyce- rides oil-based emulsion, introduced into anaesthesia practice for the induction and maintenance of anaesthesia. Its pharmacological features (rapid onset and offset, absence of cumulative effects) makes it one of the agents of choice for sedation in ICU. In paediatric practice dosage is inversely related toage. Peripheral vasodilation, negative inotropic and vagotonic properties suggest caution when propofol is administered to haemodynamically instable patients. Myoclonic acti- vity specially in children is alsoreported.Nonethelesspropofolremainsaneffective agent in the treatment of refractory status epilepticus and intracranial hyperten- sion along with barbiturates. In 1992 Parkeet al. report a fatal “propofol infusion syndrome” inPICUpatients sedated with propofol [25], followed by analogous observations [26]. The clinical course of thesyndrome includes metabolic acidosis,lipaemicserum,brady-arrhyt- mia, rhabdomyolisis, hepatic and renal failure up to death for cardiac failure unresponsive to resuscitative measures. Further reports hypothesised the disrup- tion of fatty- acid oxidation by impaired entry of long-chain acylcarnitine esters into the mitochondria and failure of the mitochondrial respiratory chain as causal mechanism [27, 28]. Despite the concerns about safe use of propofol in the PICU, Cornfield et al. speculate that propofol can be safely and effectively used for sedation in critically ill patients for extended periods of time if not exceeding 67 mg. kg –1 .h –1 [29]. Surveys in Australia/ New Zealand [30] and UK/North America [31] indicate that propofol is still used for continuous sedation in the PICU, although an unpublished randomised trial of the FDA advises against this thera- peutic practice [32]. In the PICU it is advisable to restrict the use of propofol to specific circumstances like refractory status epilepticus, increased intracranial pressure, procedural sedation. Starting doses range from 1 to 3 mg. kg –1 .h –1 [17]. Thiopental Barbiturates are classified on the basis of their chemical structure or their duration of activity. The short-actingagent thiopental (ethyl-1-methilbutyl-barbit urate,pentobar- bital) is commonly used for anaesthesia induction and endotracheal intubation. It shares with propofol the mechanism of action and the depressing effects on neurolo- gical and cardiovascolar function. This can limit its use i n haemodynamically instable patients. Moreover the barbiturate solution is alkaline, leading to incompatibility with other solutions a nd necessitating aseparateinfusion site. The m ainrole of barbiturates in the PICU is the treatment of refractory status epilepticus and of raised intracranial pressure, beyond the usefulness a s a second-line agent wh en sedation with first-line agents (BDZ a nd opioids) is i nadequate d espite inc reasing d osa ge [ 17]. Introducing continuousthiopentalsedationp rovideseffectivesedationandenablesneuromuscular blocking agents to b e discontinued. Pote ntial complications like blood pressure insta- bility, oversedation and drug reaction lead sometimes to discontinuation of the drug [33]. Starting doses range from 1 to 2 mg. kg –1 .h –1 [17]. Analgesia and sedation during mechanical ventilation in paediatrics 427 Opioids Acting on specific receptors (m, k, d) placed in the nervous system, opioids provide dose-related analgesia and some degree of sedation, without ensuring amnesia. Their combination with BDZ or propofol is advisable when amnesia is required, e.g. during neuromuscular block. The dosage of opiods is lower in newborns, for a specific sensitivity due to pharmacokinetic and pharmacodynamic reasons. Any way titration to the desired effect is necessary in every patient, as interpatient variability is common. Potentially dangerous adverse effects are frequent with opioids: respiratory depression may beof concern when partial respiratory support is given, clouding of consciousness may hamper the neurological assessment. In the PICU the widespread use of opioids refers mainly to fentanyl and morphine [3, 16]. To date evidence about the proper use of remifentanil in the PICU is not yet available. Fentanyl Fentanyl is the opioid of choice in children who undergo surgery for congenital heart disease, as its limited cardiovascular impact allows to administer it even in high dosesin this patient population. Anothereffect supporting itsuse is theability to modulate pulmonary vascular resistance and prevent pulmonary hypertensive crisis. The complication of chest-wall rigidity, specific to the syntetic opioids, is a centrally mediated reactiongenerally occurring when an high dose is givenrapidly. This phenomenon is rarely observed in the PICU, where fentanyl is usually admi- nistered by continuous infusion because of its short half-life. However fentanyl demonstrates a context-sensitive half-life, so that the duration of its effect is prolonged when it is administered over an extended period of time [17, 34, 35]. Starting doses range from 2 to 3 mg. kg –1 .h –1 [17]. Morphine Morphine is another opioid frequently used in the PICU, metabolised in the liver to morphine-6-glycuronide (M6G), an active metabolite to be excreted with urine. As compared with fentanyl, morphine can produce a potentially harmful hypotensive effect in hypovolaemic patients, due to hystaminergic vasodilation and blunting of sympathetic response and epynephrine levels. Moreover immunosuppressive ef- fects of morphine are demonstrated [36]. The binding to receptors onimmune cells involved in the inflammatory and pain response may be deleterious, though the actual role of this phenomenon in the PICU is still to be estimated. When compared to fentanyl, morphine results associated with more sedation, less chest-wall rigidity and slower developing of tolerance. Starting infusion rate is 10-30 mg. kg –1 .h –1 [17], although in newborns the initial dosage has to be reduced to 25-30% [37]. 428 M.L. Massone, L. Manfredini, G. Ottonello Ketamine Ketamine is a phencyclidine derivative acting as a NMDA (N-methyl-D-aspartate) antagonist, producing a state of “dissociative anaesthesia” by combination of a potent analgesic effect with amnesia, in the absence of depression of respiratory driving and of cardiovascular function. Favourable effects on ventilation, arterial pressure and heart rate are mediated through the release of endogenous catheco- lamines. The interaction of ketamine with opioid receptors could be the source of its dysphoric effect (vivid and unpleasant dreams). The hypothesis that ketamine should increase pulmonary vascular resistance and intracranial pressure remains controversial, although these effects seem related more to poor control of ventila- tion. Ketamine is metabolised in the liver to norketamine, an active compound which is further hydroxylated and then excreted by the kidney. Besides the currently used racemic mixture [S(+) and R (-)], the S(-) enantiomer actsasa doubly potent more selective compound, limiting the adverse effects of the original substance. Ketamine has recently been revalued, particularly in the field of regional pae- diatric anaesthesia [38]. It can play a role also in ventilated children, when sponta- neous ventilationhas tobepreserved(e.g.duringanon-invasiveapproach),in status asthmaticus, in patients adversely affected by other agents, when drug rotation is sustained during long-term sedation, as a bolus during painful procedures. Starting doses of continuous infusion are 20-80 mg. kg –1 .h –1 [38]. Combination with midazolam or promethazine is reported [17, 39]. Alfa 2 - adrenergic agonists Alfa2 - adrenoreceptors are found in the central and peripheral nervous system and in autonomic ganglia. Peripheral pre-synaptic receptors activation inhibits the release of norepinephrine, while central post-synaptic receptors stimulation inhi- bits sympathetic activity. Alfa 2- adrenergic agonists act centrally by the decrease of noradrenergic output from the locus caeruleus, resulting in an inhibitory effect leading to sedation and anxiolysis. This mechanism, including the activation of the GABA system, produces a non-REM similar sleep, the lack of which seems to be a cause of delirium during prolonged sedation by other agents (BDZ, propofol, barbiturates). Moreover analgesic properties derive to these agents from the regu- lation of substance P release, by means of a spinal cord mediated mechanism [40]. Beyond their clinical applications in the field of cardiovascular diseases (hyperten- sion) and psychiatric disorders (opiate addiction), the role of a 2- adrenergic agonists in human anaesthetic and pain relief practice has been well recognised. Adverse effects as hypotension and bradycardia are possible. Clonidine Clonidine was firstly proposed for the treatment of postoperative and oncologic pain by the epidural route, either in adults [41, 42] and in children [43]. In the last Analgesia and sedation during mechanical ventilation in paediatrics 429 decade paediatricregional anaesthesia hastaken advantage bothof its sedative and analgesic effects. Ambrose et al. found that clonidine in combination with midazo- lam at1 mg. kg –1 .h –1 is not associated with significant changesin heart rate, arterial pressure or cardiac index, beside exhibiting a significant opiod sparing effect [44]. In children with single-organ (respiratory) failure, oral clonidine at the dose of 3-5 mg. kg –1 every 8 h in combination with morphine and lorazepam, supplies a safe and effective sedation and allows opiod and benzodiazepine sparing [45]. In long-term sedation clonidine is part of differentiated cycling drug regimens [39]. Dexmedetomidine Dexmedetomidine is an a 2 -agonist drug licensed in USA by FDA for adults post- operative care sedation, characterised by an 8-fold affinity for the a 2 -adreno- ceptors than clonidine and by a favourable pharmacologic profile for the sedation of postsurgical patients during mechanical ventilation [46]. In 2001 Venn and Grounds comparedexmedetomidine with propofol in 20 adult patients requiring sedation in the first hours after surgery. They find this agent to supply a comparative depth of sedation and extubation times, with the advantage of a better quality of the sedation features [47]. The preliminary experience with dexmedetomidine in paediatrics encourages its use for sedation in mechanically ventilated children [48]. Doses range from 0.25 to 0.75 mg. kg –1 .h –1 [17]. Conclusions Providingsedationt ocri ticall yil lchil drenismandatorytosupplybothenoughcomfort and a good adaptation to the intensive care in non collaborative patients. Pharmaco- logical and non pharmacological measures suitable for the age are available. A combination ofmidazolam with fentanyl or morphine is the most extensively adopted sedation regimen in the PICU. The choice of lorazepam is limited to long-term sedation,yet therisk of accumulationof propylene-glycol should always be recalled. While recognised as safe for anaesthesia and procedural sedation, propofol is not recommended for current sedation under the age of 16, except in specific situations such as refractory status epilepticus. Barbiturates can be an alternative in these cases. Other agents like ketamine and a2- agonists may have a sparing opioid effect and are useful in the prevention and treatment of tolerance and withdrawal syndrome. So far reports on the use ofremifentanilinpaediatricsarelimitedtoanaesthesia, but its use could be advocated when rapid awakening for neurologic assessment is needed. Neuromuscular blocking agents have possible indications in PICU patients, although their administration shows controversial aspects in infants and children [49,50]. Tolerance, withdrawal and physical dependency are common after long-term 430 M.L. Massone, L. Manfredini, G. Ottonello sedation in the PICU. The awareness of this issue imposes defined strategies of prevention and treatment [51]. References 1. ACCM of SCCM (2002) Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med 30:119-141 2. Playfor SD, Thomas DA, Choonara I et al (2000)Quality of sedation during mechanical ventilation. Paed Anaesth 10(2):195-199 3. Crean P (2004) Sedation and neuromuscular blockade in paediatric intensive care; practice in the United Kingdom and North America. Paed Anaesth 14(6):439-442 4. Ambuel B, Hamlett KW, Marx CM et al (1992) Assessing distress in pediatric intensive care environments- The COMFORT Scale. J Pediatr Psychol 17:95-109 5. Marx CM, Smith PG, Lowrie LH (1994) Optimal sedation of mechanically ventilated pediatric critical care patients. Crit Care Med 22:163-170 6. van Dijk M, de Boer JB, Koot HM et al (2000) The reliability and validity of the COMFORT scale as a postoperative pain instrument in 0 to 3-year-old infants. Pain 84 (2-3):367-377 7. Ramsay MA, Savege TM, Simpson BR et al (1974) Controlled sedation with alphaxolo- ne-alphadolone. Br Med J 2:656-659 8. Parkinson L, Hughes J, Gill A et al (1997) A randomized controlled trial of sedation in the critically ill. Paed Anaesth 7:405-410 9. Ratcliffe JM (1994) Sedation in the intensive care unit. Curr Paediatr 4:106-109 10. Berkenbosch JW, Fitcher CR, Tobias JD (2002) The correlation of the Bispectral Index Monitor with clinical sedation scores during mechanical ventilation in the pediatric intensive care unit. Anesth Analg 94:506-511 11. 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Twite MD, Rashid A, Friesen RH (2004) Sedation, analgesia, and neuromuscular blockade in the pediatric intensive care unit: survey of fellowship training programs. Pediatr Crit Care Med 5 (6):521-532 17. Tobias JD (2005) Sedation and analgesia in the pediatric intensive care unit. Pediatr Ann 34(8):636-645 18. Nahara MC, McMorrow J, Jones PR et al (2000) Pharmacokinetics of midazolam in critically ill pediatric patients. Eur J Drug Metab Pharmacokinet 25(3-4):219-221 19. de Wildt SN, de Hoog M, Vinks A A et al (2003) P opulation pharmacokinetics and metabo- lism of midazolam in pediatric intensive care patients. Crit Care Med 31(7):1952-1958 Analgesia and sedation during mechanical ventilation in paediatrics 431 20. Blumer JL (1998) Clinical pharmacology of midazolam in infants and children. Clin Pharmacokinet 35(1):37-47 21. Ng E, Taddio A, Ohlsson A (2003) Intravenous midazolam infusion for sedation of infants in the neonatal intensive care unit. 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Withington DE, Decell MK, Al Ayed T (2004) A case of propofol toxicity: further evidence for a causal mechanism. Paed Anaesth 14(6):505-508 29. Cornfield DN, Tegtmeyer K, Nelson MD et al (2002) Continuous propofol infusion in 142 critically ill children. Pediatrics 110 (6):1177-1181 30. Festa M, Bowra J, Schell D (2002) Use of propofol infusion in Australian and New Zealand paediatric intensive care units. Anaesth Intensive Care 30(6):786-793 31. Playfor SD, Venkatesh K (2004) Current patterns of propofol use in PICU in theUnited Kingdom and North America. Paed Anaesth 14(6):501-504 32. Felmet K, Nguyen T, Clark RS et al (2003)The FDAwarning against prolonged sedation with propofol in children remains warranted (letter). Pediatrics 112:1002-1003 33. Yanay O, Brogan TV, Martin LD (2004) Continuous pentobarbital infusion in children is associated with high rates of complications. J Crit Care 19(3):174-178 34. Katz R, Kelly HW (1993) Pharmacokinetics of continuous infusion of fentanyl in critically ill children. Crit Care Med 21(7):995-1000 35. Ginsberg B, Howell S, Glass PS et al (1996) Pharmacokinetic model-driven infusion of fentanyl in children. Anesthesiology 85(6):1268-1275 36. Vallejo R, de Leon-Casasola O, Benyamin R (2004) Opioid therapy and immunosup- pression: a review. Am J Ther 11(5):354-365 37. Bouwmeester NJ, Hop WC, van Dijk M et al (2003) Postoperative pain in the neonate: age-related differencesinmorphine requirementsandmetabolism. IntensiveCare Med 29(11):2009-2015 38. Ivani G, Vercellino C, Tonetti F (2003) Ketamine: a new look to an old drug. Minerva Anestesiol 69:468-471 39. Jenkins I (2002) The provision of analgesia and sedation in the PICU: current practice and recent advances. Paed Anaesth 12(9):837-839 40. Maze M, Tranquilli W (1991) Alfa-2 adrenoceptor agonists: defining the role in clinical anesthesia. Anesthesiology 74:581-605 41. Filos KS, Goudas LC, Patroni O et al (1992) Intrathecal clonidine as a sole analgesic for pain relief after cesarean section. Anesthesiology 77:267-274 42. Eisenach JC, Rauck RL, Buzzanelli C et al (1989) Epidural clonidine analgesia for intractable cancer pain. Anesthesiology 71:647-652 432 M.L. Massone, L. Manfredini, G. Ottonello 43. Ansermino M,Basu R, Vandebeek Cet al (2003) Nonopioid additives to localanaesthe- tics for caudal blockade in children: a systematic review. Paediatr Anaesth 13(7):561-573 44. Ambrose C, Sale S, Howells R et al (2000) Intravenous clonidine infusion in critically ill children: dose-dependent sedative effects and cardiovascular stability. Br J Anaesth 84(6):794-796 45. Arenas-Lopez S, Riphagen S, Tibby SM et al (2004) Use of oral clonidine for sedation in ventilated paediatric intensive care patients. Intensive Care Med 30(8):1625-1629 46. Bhana N, Goa KL, McClellan KJ (2000) Dexmedetomidine. Drugs 59(2)263-270 47. Venn RM, Grounds RM (2001) Comparison between dexmedetomidine and propofol for sedation in the intensive care unit: patient and clinician perceptions. Br J Anaesth 87:684-690 48. Tobias JD, Berkenbosch JW (2004) Sedation during mechanical ventilation in infants and children: dexmedetomidine versus midazolam. South Med J 97:451-455 49. Martin LD, Bratton SL, O’Rourke P (1999) Clinical uses and controversies of neuromu- scular blocking agents in infants and children. Crit Care Med 27:1358-1368 50. Rhoney DH, Murry KR (2002) National survey on the use of sedatives and neuromu- scular blocking agents in the pediatric intensive care unit. Pediatr Crit Care Med 3(2):129-133 51. Tobias JD (2000) Tolerance, withdrawal, and physical dependency after long-term sedation and analgesia of children in the pediatric intensive care unit. Crit Care Med 28:2122-2132 Analgesia and sedation during mechanical ventilation in paediatrics 433 COMPUTING Latency reduction in clinical and translational research 1 C H. HUANG Better healthcare information technology may make better healthcare possible. However, there seems to be less penetration of information technology in health- care than in any other major industry. A recent article (Time, June 2005) summarised the e-health revolution in the past two decades. In the 1990s, software systems were developed to allowinsurance claims to be recorded and processed on computers. Products have also been developed with the aim of making it possible for doctors to run paperless medical practices; among otherthings, this involves bookingappointments online,creating e-prescriptions and, most importantly, collecting X-rays, laboratory results and medical histories in a single database accessible to physicians and patients. Using tablet PCs and examination templates, physicians can enter all the data they once wrote out by hand, leaving more quality time to spend with the patients. These medical records can then be viewed by the patients at home via their doctor’s website. Websites are also developed to manage family’s health history. Informa- tion can be collected, stored and shared with any physician who is taking part in the programme. Hardware devices are also being developed to facilitate portable, accessible records. For example, patients can get the results of physical examina- tions and ECGs and other data loaded onto a thumb drive that plugs into a PC. Records can be updated on visits to specialists and beamed to other doctors. Patients can also download personal information, such as details of allergies, previous surgery, chronic conditions, and the drugs they are currently taking onto a smart card. Such cards could be life-saving when emergencies occur away from patients’ normal areas. The establishment of regional health information organisations is another step forward. An organisation of this type serves patients, and also area doctors, hospi- tals, laboratories, pharmacies, insurers, employers and consumers. If a resident makes an emergency-room (ER) visit on a Saturday, the ER doctor can call up the patient’s records from his or her primary care physician. There are risks involved in computerising personal healthinformation,andprivacyadvocatesareespecially concerned that once patient records are online it will be much easier for sensitive information to fall into the hands of, say, insurance companies or potential em- ployers. Yet, since regional health organisations came into being, the medical Chapter 40 1 This research has beensupported in part by anNSF (USA) grant (CNS-0551549) and anNIH (USA) grant (LM-008619). community has been rapidly plugging into the new world of electronic health records. Healthcare-related research and practice often produce tremendous amounts of data. These data are usually geographically distributed among hospitals, clinics, research laboratories, radiology centres, etc. For research, training or clinical purposes, physicians and medical researchers often need to consult and analyse medical data from various different sites. The on-demand integration/extraction and automated analysis of these data in a real-time manner will yield a significant level of convenien ce and is therefore increasingly needed. However, owing to the sensitive nature of these data and the lack of an effective and flexible integration approach, medical data are currently often stored and archived inside each data producer (hospitals, clinics, laboratories, etc.), and are usually disconnected from the outside world to enforce security issues. The massive computing power that can now be accessed can be applied to help doctors in making diagnoses and treatment decisions. With the advent of the internet, it became possible, theoretically, to communicate new standard practices to doctors within months rather than 15 years, which is the current lag-time between discovery and practice. In addition, pharmaceutical companies with ac- cess to anonymous health data could improve and speed up drug development. The dynamic networking technology of today will have the potential to allow hospitals in rural areas to access expensive medical equipment in peer medical institutes securely in a real-time manner. All this sheds light on a new generation of e-health that could potentially improve healthcare quality. Grids represent a rapidly emerging and expanding technology that allows geo- graphically distributed resources (CPU cycles, data storage, sensors, visualisation devices, and a wide variety of internet-ready instruments) that are under distinct control to be linked together in a transparent fashion. The power of the grid lies not only in the aggregate computing power, data storage and network bandwidth that can readily be brought to bear on a particular problem, but in its ease of use. Since resources in a grid are pooled from many different domains, each with its own security protocol, ensuring the security of each system on the grid is of paramount importance. The potential of the grids for serving as a general-purpose research platform also results from the following facts, as pointed out in [1]: – The internet is reasonably mature and able to serve as a fundamental infra- structure. – Network bandwidth hasincreasedtothe point of being able toprovide efficient and reliable services. – Storage capacity has now reached commodity levels where a terabyte of disk can be purchased for roughly the same price as a high-end PC. – More and more instruments are becoming Internet aware. – Clusters, supercomputers, storage and visualisation devices are becoming more easily accessible. – Applications have been parallelised. – Collaborative environments are moving out of the alpha phase of implemen- tation. 438 C H. Huang [...]... ill hospitalized patients JAMA 274:159 1-1 598 3 Donchin Y, Gopher D, Olin M et al (1995) A look into the nature and causes of human errors in the intensive care unit Crit Care Med 23:29 4-3 00 4 Miller PA (2001) Nurse-physician collaboration in an intensive care unit Am J Crit Care 10: 34 1-3 50 5 Rapoport J, Teres D, Steingrub J et al (2000) Patient characteristics and ICU organizational factors that influence... II and LOD scores for predicting hospital mortality in ICU patients hospitalized more than 72 h Intensive Care Med 6 :101 2-1 021 32 Metnitz PG, Moreno RP, Almeida E et al (2005) SAPS III: from evaluation of the patient to the evaluation of ICU, part 1 Intensive Care Med 10: 133 6-1 344 33 Moreno RP, Metnitz PG, Almeida E et al (2005) SAPS III: from evaluation of the patient to the evaluation of ICU, part. .. (1) Tele-systems for diagnostic, prognostic and therapeutic applications (2) Health data storage and retrieval (3) Social healthcare (4) Pharmaceutics and clinical trials (5) Computerised epidemiology (6) Collaborative and proprietary health grids (7) Data mining and visualisation of health data (8) Text mining of healthcare information bases (9) Healthcare information retrieval and integration (10) Distributed... computational and data grid In: Proceedings of the 4th IEEE/ACM Symposium on Cluster Computing and the Grid—BioGrid Workshop, CD-ROM 2 Huang C-H (2005) Bio-Grid: bridging life science and information technology In: Proceedings of the 5th IEEE/ACM Symposium on Cluster Computing and the Grid (BioGrid Workshop), CD-ROM 3 Huang C-H, Lanza V, Rajasekaran S, Dubitzky W (2005) HealthGrid: towards collaborative and on-demand... part 2 Intensive Care Med 10: 134 5-1 355 34 Zimmerman JF, Kramer AA, McNair DS et al (2006) Acute physiologies and chronic health evaluation (APACHE IV): hospital mortality assessment for today’s critically ill patients Crit Care Med 85:153 8-1 539 35 Garland A (2005) Improving the ICU Chest 127:215 1-2 164 36 Boffelli S, Rossi C, Anguileri A et al (2006) Continuous quality improvement in intensive care Medicine... Institute for Supercomputing and Visualization (CISV, under BECAT at UConn), and also to additional computing resources off campus, including Latency reduction in clinical and translational research 445 - A 64-processor SGI Altix 3700 The newly purchased and installed SGI Altix system consists of (1) an 8-processor SGI Altix 350 with 8 GB memory as the front-end server and (2) a 64-processor SGI Altix 3700... 283:255 9-2 567 6 Azoulay E, Chevret S, Leleu G et al (2000) Half the families of intensive care unit patients experience inadequate communication with physicians Crit Care Med 28:304 4-3 049 7 Eggimann P, Pittet D (2001) Infection control in the ICU Chest 120:205 9-2 209 8 Angus DC (1998) Grappling with intensive care unit quality: does the readmission rate tell us anything? Crit Care Med 26:177 9-1 780 9... 16 Knaus WA, Le Gall JR, Wagner DP et al (1982) A comparison of intensive care in the USA and France Lancet II:64 2-6 46 17 Le Gall JR, Loirat P (1995) Can we evaluate the performance of an Intensive Care Unit? Curr Opin Crit Care 1:21 9-2 20 18 Ridley S (1998) Severity of illness scoring systems and performance appraisal Anaesthesia 12:118 5-1 194 464 J.R Le Gall 19 Lemeshow S, Le Gall JR (1994) Modeling... in pre-hospital trauma resuscitation, the so-called lethal triad (coagulopathy, acidosis and hypothermia) is a challenge to the intensive care doctor in terms of early recognition and treatment of these dreadful complications [5] Prevention of hypothermia by keeping the patient dry and covered is mandatory in the pre-hospital setting; the patient should also be provided with a warm environment and warmed... randomised trials on trauma and ICH patients have recently been published In the randomised double-blind trial on bleeding control in severely injured trauma patients, Boffard et al [24] demonstrated the partial efficacy and safety of rFVIIa Patients with severe trauma were randomised to a placebo group or to a rFVIIa group in which they received three intravenous injection boluses of 200, 100 and 100 . of sedation in the critically ill. Paed Anaesth 7:40 5-4 10 9. Ratcliffe JM (1994) Sedation in the intensive care unit. Curr Paediatr 4 :10 6-1 09 10. Berkenbosch JW, Fitcher CR, Tobias JD (2002) The. 25( 3-4 ):21 9-2 21 19. de Wildt SN, de Hoog M, Vinks A A et al (2003) P opulation pharmacokinetics and metabo- lism of midazolam in pediatric intensive care patients. Crit Care Med 31(7):195 2-1 958 Analgesia. Australian and New Zealand paediatric intensive care units. Anaesth Intensive Care 30(6):78 6-7 93 31. Playfor SD, Venkatesh K (2004) Current patterns of propofol use in PICU in theUnited Kingdom and