2 g of 2% paste or gel 2 g of 2% paste or gel 2 g of 4% paste or gel 2 g of 2% paste or gel 2 g of 2% paste or gel 2 g of 4% paste or gel 2 g of 2% paste or gel 2 g of 2% paste or gel 2 g of 4% paste or gel B. Gut AGNB: polymyxin E (mg) with tobramycin (mg) Yeasts : amphotericin B (mg) or nystatin (units) MRSA: vancomycin (mg) 100 80 500 2 \227 106 20 \200\22340/kg 200 160 1000 4 \227 106 20 \200\22340/kg 400 320 2000 8 \227 106 500 \200\2232000 2. Parenteral antimicrobials: \200\230normal \200\231 PPM cefotaxime (mg) 150/kg 200/kg 4000 3. Hygiene 4. Surveillance cultures of throat and rectum on admission, Monday, Thursday 476 G MARX & K REINHART Markers of infection \200 Tips of in-dwelling catheters. Microbiological investigation of any drainage fluid availabl e. Radiological investigation (CXR or a CT scan) searching a focus. Echocardiogram to exclu de endocarditis. Dental status excluding an odontogenous focus. The diagnosis of infection in the ICU patient may be obvi- ous or extremely dif \201 cult. Infection, and especially sepsis, is a leading cause of death and the main cost driver in ICUs. Epidemiologic data show that sepsis is the third most fre- quent cause of death after coronary heart disease and MI in Germany. The \201 rst clinical signs of infection or se psis are usually non-speci \201 c (e.g. fever or leucocytosis). More speci \201 c symptom s, such as arterial hypotension or raised lactate, often indicate progression to organ dysf unction associated with an increased mortality rate of 35 \200\22370%. The ideal infection/ sepsis marker has high sensitivity and speci \201 city, easy handling and low costs. The m arker should be able to indicate the stages of the disease and the prog- nosis of the patie nt. The in \202 ammatory reaction consists of humoral, cellular and molecular pathways. Ch anges in body temperature, leucocyte count, heart rate, blood pressure and respiration rate are clinical signs of systemic in \202 ammation. They are neither speci \201 c nor sensi tive for sepsis and also occur in non-infectious states. Generalized in \202 ammation with organ dysfunction (systemic in \202 ammatory response syndrome) may also result from panc reatitis, major trauma and burns. The American College of Chest Physicians/Society of Criti cal Care Medicine consensus criteria are not helpful for clinical differentiation at the be dside. Ideally, an infec- tion marker should meet the following demands: 1 Shorten the time to and accuracy of diagnosis 2 Facilitate the differentiation between infectious and non- infectious causes of in \202 ammation and its sequelae \200\224 organ dysfunction or shock \200 Special investigations \200 Procalcitonin (PCT): bacterial endotoxins are a major stimulus for PCT induction, but Gram- positive infections may also induce a PCT release and may be detected within 2h of endotoxa emia or bacteraemia. During severe fungal infections, PCT induction has been described in s ome patients. However, major surgery, severe trauma or burns may also induce an increase of PCT plasma levels, although usually not as high as in patients with severe sepsis or septi c shock. A number of studies con \201 rm PCT as a marker of severe infections and sepsis. Those with PCT levels \211 0.5ng/ml are unlikely to have severe sepsis or septic shock, wh ereas levels >2ng/ml identify patients at high risk. PCT concentra- tions >10ng/ml usually occur in patients with organ fail- ure remote from the site of infection. When PCT is relea sed non-speci \201 cally because of major surgery or severe trauma, daily monitoring may b e helpful to detect supervening septic complications early. CRP is an acute-phase protein t hat is released from hepatic cells after stimulation by in \202 ammatory media- tors such as IL-6 and IL-8. The value of high plasma levels of CRP in diagnosing patients with infect ion and sepsis or the assessment of sepsis severity is controversial. CRP may not peak not till 48h. Circulating CRP increases dur- ing minor infections, does not correlate with the severity of host response and does not differentiate between survivors and non-survivors of sepsis. CRP plasma levels may remain elevated up to several days, and it is found in many non-infectious conditions, such as autoimmune and rheumatic disorders, ACS and malignant tu mors, and after surgery. Endotoxin (LPS) is an essential structure in the outer cell membra ne of Gram-negative bacteria. The Limulus amoebocyte lysate assay was problematic, with wid e variation in value, low speci \201 city (due to differences in the endotoxin structure i n different bacteria) and interactions with plasma proteins and antibiotics. A new highly s ensitive ex vivo biological assay will soon be available. It measures the zymosan antibody- and antien- dotoxin antibody-elicited respiratory burst in a kinetic luminometric assay. I t has a high negative predictive value for the diagnosis of Gram-negative infection and sep sis, with a sensitivity of 85.3% and a speci \201 city of 44%. The endotoxin activity essa y has promise for Gram-negative infection. 3 Allow differentiation between underlying viral and bac- terial infections 4 Re \202 ect the effectiveness of antimicrobial treatment and other measures of source co ntrol more accurately than conventional clinical and laboratory signs. Clinical approach Once infection is suspected in the ICU patient, the goal is to identify t he infecting pathogen. History: key points \200 Past medical history to identify previous infections and co-morbidities) recently used anti microbial therapy, recent medical interventions or the risk for colonization/ infection wit h resistant organisms. Mental state. Septic encephalopathy is one of the most commonly miss ed initial signs of an infection. Examination and investigation: key points \200 Clinical opinion to con \201 rm diagnosis by measuring tem- perature, respiratory rate, he art rate and blood pressure, examination of CNS, thorax, heart, lung, abdomen, kidney or an y other susceptible area. FBC to measure the WCC. Blood specimen (2 \200\2233 blood aerobic and anaerobic cultures). Urine specimen to exclude UTI. Bronchoalveolar lavage (BAL) or tr acheal secretions and direct examination of BAL specimen using Gram staining for the diagno sis of pneumonia. Feces in the presence of diarrhea, Other specimen (CSF, exudates, swabs o f mucous membranes). \200 Clinical diagnostic dif \201 culties to consider In sepsis, blood cultures are positive in 30 \200\22340% of those with sepsis and with false positives. Positive results may indica te colonization or contamination without pathophys- iological relevance. Microbiological di agnosis may be dif \201 - cult in patients with prior antibiotic treatment. In 35%, sepsis cannot be proved microbiologically despite the pres- ence of clinical signs and suspicion of a focus. \200 \200 477 CHAPTER 27.8 Markers of infection Diagnosis of special infections Ventilator-associated pneumonia The diagnosis of VAP is dif \201 cult since there is no accurate diagnostic criterion which reliably differentiates p neumo- nia from non-infectious causes of pulmonary in \201 ltration. Interpretation of mic robiological \201 ndings is hampered by the high rate of colonization in mechanically ven tilated patients. The International Sepsis Forum recommends the use of the Clinical Pulmona ry Infection Score (CPIS) for the diagnosis of VAP (CPIS >6). The score is based on body te mperature, WCC, volume and appearance of tracheal secretions, oxygenation (PAO2/FIO2), CXR and tracheal aspirate cultures. The CPIS allows for a standardized diag- nosis by using sim ple clinical end-points. In a clinical study, the CPIS was able to diagnose pneumonia with a sensitivity of 93% and a speci \201 city of 100%. obscure to many physicians. The clinical \201 ndings can be subtle and misleading, contri buting to delayed diagnosis. It must be excluded in all septic patients with an unknown foc us presenting with right upper quadrant tenderness and pain and pathological cholestatic pa rameters. For the diagnosis, laboratory investigations (PCT), blood cultures, abdominal ult rasonography and abdominal CT scan are required. Invasive Candida infection The incidence of invasive Candida infection is 1 \200\2232% in ICU patients. The gold standard for diagnosis of an invasive Candida infection is the histo pathological or cytopathological proof in the suspected tissue areas or in usual sterile bo dy \202 uids, but not the urine. Routine screen- ing to identify Candida colonization, wh ich is present in 16% of ICU patients, is not recommended. Neutropenic, immune-compromised or immune-suppressed patient as well as patients after major abdominal surgery are at high er risk of developing a Candida infection. Catheter-induced infection Again dif \201 cult. A catheter-induced infection cannot be dia g- nosed without the removal of the catheter. If a CVC is a potential source of infection, it needs to be removed to be tested. Blood cultures should be taken from the CVC before rem oval, plus a peripheral blood culture. Swabs should be taken from the insertion site. If in fection is suspected, change of the CVC via the guide wire is not recommended. As routine c hange of CVC does not reduce the risk of bacteraemia, CVC change should be performed in the presence of suspected infection, not routinely. Support group German Sepsis Society <www.dsg.de.>, Tel. +49-3641- 9323101. Expert adviser Professor K. Reinhart, Head of Department, Clinic for Anesthesiology and Int ensive Care, D-07747 Jena, Germany Further reading Abraham E, Matthay MA, Dinarello CA, et al. Consensus confer- ence de \201 nitions for sepsis, septic shock, acute lung injury, and acute respiratory distress syndro me: time for a re-evaluation. Crit Care Med 2000; 28: 232 \200\2235. Wound infection In the presence of a wound infection, blood cultures are recommended. Ultra sonography-guided diagnostic punc- ture for \202 uid under a closed wound, or taking swab s from the suspected area enables microbiological diagnosis. A Gram stain, and aerobic and anaerobic microbiological cultures are recommended. Clinical Pulmonary Infection Score (CPIS): Am. J. Respir. Crit. Care Med., Volume 168, Number 2, July 2003, 173 \200\223179. Engel C, Brunkhorst FM, Bone HG, et al. Epidemiology of sepsis in Germany: results from a n ational prospective multicenter study. Intensive Care Med 2007; 33: 606 \200\22318. Intra-abdominal sepsis Classical clinical and laboratory \201 ndings of intra-abdominal p athologies include fever, leucocytosis, elevated PCT and localized abdominal tenderness. Po st-operative abscesses are dif \201 cult to diagnose because these signs are often present after abdominal surgery in patients without abscesses. Abdominal CT scan using contrast is the ulti- mate diagnostic intervention for diagnosis. Reduced mor- tality from intra-abdom inal sepsis is attributed to early diagnosis using CT scanning rather than any improvement in the therapy of MOF. Meisner M, ed. Procalcitonin (PCT): a new innovative infection parameter. Biochemical and c linical aspects, 3rd revised and extended edn. Stuttgart; Georg Thieme Verlag, 2000. Pugin J, Auckenthaler R, Mili N, et al. Diagnosis of ventilator-associated pneumonia by bac teriologic analysis of bronchoscopic and nonbronchoscopic \200\230blind \200\231 bronchoal veolar lavage \202 uid. Am Rev Respir Dis 1991; 143: 1121 \200\2239. Ugarte H, Silva E, Mercan D, et al. Procalcitonin used as a marker of infection in the inte nsive care unit. Crit Care Med 1999; 27: 498 \200\223504. Acute acalculous cholecystitis Acute acalculous cholecystitis is marked by a very high mort ality rate, but its relative rarity makes its features 478 D ANNANE & C SPRUNG Adrenal insuf \201 ciency and sepsis Adrenal insuf \201 ciency is a condition in which cortisol syn- thesis, delivery and/or up take by tissues is compromised. It is classi \201 ed into: 1 Primary adrenal insuf \201 c iency when the adrenocortical cells are damaged or cortisol metabolism is altered. 2 Second ary adrenal insuf \201 ciency when corticotro phin releasing hormone or adrenocorticotroph in hormones synthesizing hypothalamic or pituitary cells are damaged. A recent study in sev ere sepsis/septic shock suggested that adrenal insuf \201 ciency may reach 60%. Special investigations Random cortisol If the serum albumin <25g/l, total cortisol levels m ay be unreliable; calculate free cortisol. Random cortisol <3mcg/dl De \201 nite <10mcg/dl Maybe. >44mcg/dl Not Mechanisms of action of glucocorticoids Glucocorticoids act through genomic and non-genomic effects. \200 If cortisol levels are low, ACTH levels can discriminate between primary (high ACTH levels) and secondary adre- nal insuf \201 ciency (low ACTH levels). Genomic effects: glucocorticoid is involved in regulation of gene transcription by nuclear receptors including genes for chemokines, cytokines, complement family members and innate i mmune-related genes, including scavenger and TLRs. Non-speci \201 c non-genomic effects: m embrane effects of glucocorticoids in the hypothalamic synaptosomes affect sympathetic modu lation of cardiac and blood vessel activity, as well as the potentiation of exogenous cate- cholamines. Speci \201 c non-genomic effects: enhanced endothelial NOS activation. ACTH test 250mcg of synthetic corticotrophin. cortisol levels >44mcg/dl or cortisol increme nt >16.8mc/ dl rules out adrenal insuf \201 ciency. Clinical consequences Initial course of critical illness. \200 Fluid and vasopressor unresponsiveness with low vascu- lar resistance and high cardiac inde x Systemic in \202 ammatory response syndrome with fever, tachycardia, tachypnea Multiple organ failure Increased risk of death from refractory shock Main effects of glucocorticoids Metabolic effects Increase blood glucose concentrations by inducing systemic insulin resistance, liver gluconeogenesis and glycogenolysis. Enhance lip olysis and proteolysis, providing amino acids for neoglucogenesis. \200 Late course of critical illness, \200 Vasopressor dependency \200 Ventilator dependency \200 Multiple organ failure \200 Increased risk of death from multiple organ failure Immune effects \200 Innate immunity: increase neutrophils, promote apopto- sis of eosinophils and basophils, im prove opsonization and the activity of the scavenger system. Suppress the synthesis of in \202 ammatory mediators such as cytokines, prostaglandins and leukotrienes. Adaptative immu nity: prevent differentiation of CD4+ T cells into T helper (Th)1 lymphocytes, promote Th2 recruitment by increasing IL-10 secretion acting in syn- ergy with IL-4. Thus, glucocortico ids induce a shift from a cellular toward a humoral immune response. Management Fluid and sodium losses should be managed with \202 uid and vasopressors, whic h should be titrated to restore SBP and tissue perfusion. Practical modalities of hormonal treatment in sepsis Steroids are indicated in adult septic shock patients whose blood pressure is poorly responsive to \202 uid resuscitation and v asopressor therapy. Not in the rest. Cardiovascular effects Maintain vascular tone, endothelium integrity, capillary per- meabil ity and myocardial inotropic activity. Synergistic with norepinephrine and angiotensin II. In catecholamine- treated septic shock, glucocorticoids improve SVR and hasten shock revers al. Treatment \200 \200 Hydrocortisone at a daily dose of 200 \200\223300mg. Treatment should be continued as long as the clinical consequences have disappeared. Prolonged treatment requires advice from an endocrinologist. Administration of fludrocortisone is optional and requires advice from an endocrinologist. Clinical approach Examination: non-speci \201 c signs \200 Hypotension, shock (90%) \200 Fever (60-70%) \200 Abdominal pain, distension (80 \200\22390%) \200 Vomiting (50 %). \200 Confusion to coma (40 \200\22360%) Surveillance It is paramount that surveillance includes: \200 \200 \200 blood glucose <150mg/dl serum sodium screening for infection. (hydrocortisone blunts the fe brile response and interferes with WCC and in \202 am- matory parameters.) 479 CHAPTER 27.9 Adrenal insuf \201 ciency and sepsis Further reading Annane D, Maxime V, Ibrahim F, et al. Diagnosis of adrenal insuf \201 - ci ency in severe sepsis and septic shock. Am J Respir Crit Care Med 2006; 174: 1319 \200\2232 6. Lipiner-Friedman D, Sprung CL, Laterre PF, et al. for the Corticus Study Group. Adrenal fun ction in sepsis: the Corticus Retrospective Cohort Study. Crit Care Med 2007; 35: 1012 \200 \2238. Hamrahian AH, Oseni TS, Arafah BM. Measurements of serum free cortisol in critically ill pa tients. N Engl J Med 2004; 350: 1629 \200\22338. This page intentionally left blank 481 Chapter 28 Trauma and burns Chapter Contents Initial management of major trauma 482 Head injury 484 Spinal trauma 486 Chest trauma 488 P elvic trauma 490 Burns \200\224 \202 uid management 492 Burns \200\224general management 4 94 482 B WINTER, S SARKAR, & H PATTANI Initial management of major trauma The cervical spine is assumed to be injured in all victims of blunt trauma, and either the \200\230holy trinity \200\231 of hard collar, head blocks and tape/straps, or manual in-li ne immobiliza- tion until injury is ruled out. Major trauma remains a leading cause of death in both the developed and developing worlds, and has a signi \201 cant impact on the workload of most critical care units. More people are disabled than killed, which has a signi \201 cant impact on the economic potential of both the victims and society. The most common method of initial management follows the prin ciples espoused by the Advanced Trauma Life Support (ATLS ) course of the American Colle ge of Surgeons. This course was started following an airplane crash in 1977 in which the fa mily of James Styner (an ortho- paedic surgeon working in Lincoln, Nebraska) was seri- ousl y injured. The management was so disorganized that, with colleagues, a course initially was devised to improve trauma care. This course, the ATLS course, spread across the USA and then internationally. The underpinning principle was the presumed tri-modal death distribut ion for major trauma, although this has been questioned in the UK where most trauma is made up of road traf \201 c accidents. This concept proposes that there are a number of deaths immediately after trauma which are not amenable to medical intervention, a second peak of poten- tially avoidable deaths (the golden hour) and then those deaths occurring later, oft en in a critical care setting. Predictors of death during the early period of trauma care i nclude age of the patient, presence of isolated neuro- logical damage, base excess, hemoglo bin level and the triage revised trauma score. Trauma scoring is used as a means of describ ing injury severity, predicting patient outcomes and evaluating aspects of care. The scorin g systems vary, with some using physiological variables (GCS, Revised Trauma Score), and ot hers anatomical injury (Abbreviated Injury Score, Injury Severity Score). In the UK, the Tr auma Audit and Research Network coordinates the audit of patient outcomes in a similar way to that of ICNARC and publishes outcomes on its website (www. uktarn.ac.uk). Priorities in the golden hour revolve around the ABCDE resuscitation principles common to many of the lif e sup- port courses. In this context, ABCDE translates into: 1 Airway maintenance with cerv ical spine protection 2 Breathing and ventilation 3 Circulation with hemorrhage control 4 D isability: neurological status 5 Exposure/environmental control In addition, the concept of primary and secondary surveys was introduced. In the primary survey, the immediately life- threatening interventions are identi \201 ed and dealed with using mainly clinical skills, with the addition of adjuncts. The management of the patient in the primary survey focuses on symptom and sign detection and their treatment, with less focus on the detail of diagno sis. B There have traditionally been six \200\230immediately life- threatening \200\231 injurie s taught using the acronym ATOM FC. \200 \200 \200 \200 \200 \200 Airway obstruction Tension pneumothorax Open pneumothorax Massive haemothorax Flail chest C ardiac tamponade Thoracic trauma comprises 10 \200\22315% of all trauma and is the cause of death in 25% of all fatalities due to trauma. The mortality increases if there are>6 broken ribs, but this effect is reduced by the use of epidural analgesia. Pulmonary contusion underlying a \202 ail chest or in isolation is the most common injury requiring ongoing ventilation in a cri tical care unit, and is treated as for any other lung injury with appropriate use of PEEP. C By far the most common cause of haemodynamic disturbance in the early phase of trauma man agement is hemorrhage. Volume of blood loss can be assessed using the acronym one on the \202 oor and four more; pelvis, chest, abdomen and long bones. The degree of shock in the e arly phase is often assessed using a grading system such as the ATLS system that is based on the physiological distur- bance related to the volume of estimated blood loss. Using th is system, easily remembered from tennis scores, shock is graded from grade 1 (0 \200\22315 % blood loss), through grade 2 (15 \200\22330%), grade 3 (30 \200\22340%) to grade 4 (>40% blood loss). Of note, SBP does not fall until grade 3 although the pulse pressure narrows a s vasoconstriction raises the diastolic pressure. Both base de \201 cit and lactate have b een suggested as a monitor of the extent of shock. Minimizing the time from injury to opera tive intervention has been shown to reduce the mortality in shocked trauma patients. Adjunc ts such as radiology of chest and pelvis and abdomi- nal ultrasound (Focused Abdominal Scan for Trauma, FAST) for haemorrhagic shock may add diagnostic information, which mandates th e patient going to theater during the C of the primary survey. Using modern 16-slice CT sca nners, total whole-body scanning time is 120s. 64-slice CT scan- ners may reduce scanning time to <30s, although time to interpret the scans remains the same. If the scanner is adja - cent to the emergency department, then CT scans provide more accurate diagnostic informat ion, but unstable patients should go straight for operative intervention. Bleeding from pel vic injury is best controlled with a combi- nation of pelvic closure, using external \201 xators or binders, and angiographic embolization, although pelvic packing may also have a place. Damage control laparotomy is increasingly employed to avoid the cold, coagulopathic and acidotic patient resistant to resuscitation. Control of bleeding and contamination is a chieved and then the patient is admitted to the critical A The airway is secured in a standardized way regardless of the underlying cause of obstruc tion. If the airway requires intubation to be performed, then capnography should be availab le to con \201 rm tube placement. 483 CHAPTER 28.1 Initial management of major trauma Further reading Bickell WH, Wall MJ, Pepe PE, et al. Immediate versus delayed \202 uid re suscitation for hypotensive patients with penetrating torso injuries. N Engl J Med 199427; 331: 1105 \200\2239. care unit to be \202 uid resuscitated, warmed and optimized with temporary closure of the abdomen. The patient is then returned to theater for de \201 nitive repair of injury once stable. There is an increasing drive for \200\230permissive hypotension \200\231 in the s hocked bleeding patient, with the aim in the short term of resuscitation to maintain life b ut avoid exces- sive volumes and the risk of clot disruption until control of hemorrhage ha s been achieved. The only good evidence relates to penetrating truncal trauma in an urban s etting, but the tendency is to resuscitate to an end-point of a pal- pable radial pulse unt il control of bleeding has been gained. Additional therapies such as early administration o f clot- ting factors and other agents such as anti \201 brinolytics and activated VIIa may also have a place in the treatment of major hemorrhage. Cales RH, Trunkey DD. Preventable trauma deaths. A review of trauma care systems developmen t. JAMA 1985; 254: 1059 \200\22363. Flagel BT, Luchette FA, Reed RL, et al. Half-a-dozen ri bs: the break- point for mortality. Surgery 2005; 138: 717 \200\22325. Janjua KJ, Sugrue M, Deane SA. Prospective evaluation of missed injuries and the role of te rtiary trauma survey. J Trauma 1998; 44: 1001 \200\2236. Lichtveld RA, Panhuizen IF, Smit RBJ, et al. Predictors of death in trauma patients who are alive on arrival at hospital. Eur J Trauma Emerg Surg 2007; 1: 46 \200\22351. Mackenzie R, Bevan D. Is the \200\230golden hour \200\231 a prehospital event? Emerg Med J 2005; 22: e1. Martinowitz U, Kenet G, Segal E, et al. Recombinant activated factor VII for adjunctive hem orrhage control in trauma J Trauma 2001; 51: 431 \200\2239. D Head injury accounts for 25% of trauma deaths. Morbidity and mortality are substantially increased by hypoxia and hypotension. Signs of an intracerebral haematoma such as unilatera l pupil dilatation or lateralizing signs may be an indication for a CT scan for brain injur y in D of the primary survey. This should only be performed if life-threatening hemorrhage has been treated or ruled out. Spahn CR, Cerny V, Coats TJ, et al. Management of bleeding follow- ing major trauma: a Euro pean guideline. Crit Care 2007; 11: R17 Ziegler DW, Agarwal NN. The morbidity and mortality of rib fractures. J Trauma 1994; 37: 975 \200\2239. E The \201 nal stage of the primary survey is complete expo- sure of the patient with car e taken to not render them hypothermic. Once the primary survey has been completed and the patient is improving, then a secondary survey is initiated with the aim of detecting all po tential threats to life and any other injuries that may threaten the patient \200\231s retu rn to full activity. In the context of critical care where the patient is usually sedated, the major missed injuries include liga- ment injuries in the knee, compartment syndromes an d fractures of the small bones in the foot or hand. Some have proposed a tertiary survey to minimize these. Missed inju- ries are more common in those patients with a prolonged criti cal care stay. Fig. 28.1.1 Example of a ruptured diaphragm. 484 M MACMAHON & P ANDREWS Head injury De \201 nition Head injury is traditionally divided into mild, moderate and severe based u pon the GCS (13 \200\22315, 8 \200\22313 and <8, respectively). Clinical management Initial assessment and immediate management This should be based upon A TLS principles. The assess- ment of disability should include the GCS, which provides a fra mework for assessment, and guides therapeutic man- agement, further investigation and progn osis. Assessment of pupillary size and reactivity also gives valuable informa- tion on ICP and focal intracranial injuries. The decision to intubate and ventilate will depend upon th e GCS (including deterioration) and the need for airway protection, the extent of other inj uries and the need for transfer for investigation/de \201 nitive management. As a gen- era l rule, failure to obey commands, to maintain good oxy- genation and normocapnoea, or confu sed and combative behavior should lead to a decision to intubate using a rapid sequence ind uction and manual in-line stabilization of the cervical spine. Incidence The estimated incidence of major head injury, or traumatic brain injury (TBI) is between 100 and 400 per 100 000 capita. Worldwide that correlates with 1 in 8 deaths in men and 1 in 14 deaths in women. Epidemiology Head injury represents a major cause of death and long- term disability in you ng and old, with the subgroup of young men at a particularly high risk. The majority of sev ere head injuries in the UK are associated with road traf \201 c accidents and commonly in volve trauma to multiple organ systems. Primary brain injury The primary injury is caused by axial loading and shearing forces on t he individual axons within the brain. This is referred to as diffuse axonal injury (DAI). R adiologically this appears as diffuse brain swelling and loss of gray \200\223white differe ntiation on CT imaging. There may also be focal changes evident commonly in frontal, tempor al and occipi- tal regions, referred to as contusions. Primary brain injuries may be associ ated with injury to the arterial, venous and capillary vasculature. This can cause extradur al, subdural and intraparenchymal haematomas. Investigation, referral, transfer and surgical intervention Early de \201 nitive imaging a llows identi \201 cation of acute trau- matic intracranial injury and improves outcome. It also guides decisions about the intensity and length of observa- tion in low risk cases. T he decision to perform a CT scan in mild/minor head injury will depend upon local resources and protocols. Transfer to a specialist neurological center will provide access to the ski lls and facilities for intracranial surgery and the availability of advanced monitoring and guided medical management. Features mandating discussion with a neuro- surgeon include: \200 Secondary brain injury There are several mechanisms by which the injured brain suffers a se condary injury. These can be divided into two categories. CT scan in a general hospital shows an acute intracranial lesion. When a patient ful \201 ls criteria for a CT scan, but this cannot be performed urgently. When a patient has clinic al features suggesting specialist care is appropriate (whatever the result of the CT scan). These include; \200 The failure of adequate oxygen delivery Brain oxygen delivery is governed by the following principles; \200 Cerebral oxygen delivery = Blood oxygen content x Blood Flow ( \210\236PaCO2) Blood oxygen content = hemoglobin level x 1.32 x % oxygen saturation Cerebral perfusion pressure = mean arterial pressure \200\223 intracranial pressure Persisting coma (GCS <9) and no eye opening after initial resuscitation Confusion persistin g >4h Deterioration in conscious level Persistent focal neurological signs A seizure withou t full recovery Compound depressed skull fracture De \201 nite or suspected penetrating br ain injury CSF leak or other sign of a skull fracture. \200 \200 \200 \200 \200 \200 Manipulation of the parameters in bold will improve oxy- gen delivery to the cerebrum as a whole. Cerebral blood \202 ow per se will depend upon the resis- tance of the vessels in question and cardiac output, in addi- tion to the CPP. It is the vessel resistance and capa citance that vary with \202 uctuations in PaCO2. Delivery must be equal to or in excess o f oxygen con- sumption. The major determinant of consumption is the cerebral metabolic rate . \200 Intensive care Neurological intensive care is based upon the optimization of physiological parameters. The goals are a CPP of >60mm Hg and an ICP of <20mm Hg. Techniques for reducing ICP are considered double-edged swords, and pursuit of arbitrary levels has the potential to have a negative impact on brain recovery. It has been sug- gested that more advanced mon itoring techniques could bet- ter guide therapeutic intervention and possibly reduce harm. Cerebral metabolic rate; increased with seizures and pyrexia, reduced with sedation. At the cellular level, changes in oxygen uptake and utiliza- tion may be responsible for th e ischaemic areas that are demonstrated despite optimization of global oxygen delivery. Monitoring Intracranial pressure A pressure transducer inserted into the non-dominant cere- bral hemisphere (intraparenchymal) is the most commonly used site in the UK. This gives a continuous, reliable and Post-trauma, cell injury mechanisms These include excitotoxicity, in \202 ammation, pyrexi a, hyper- glycaemia, apoptosis and free radical damage. 485 CHAPTER 28.2 Head injury rapidly responsive estimation of ICP. Intraventricular cathe- ters are the gold standard an d they allow sampling of CSF. However, they are associated with an increased risk of infect ion, particularly when used for periods >7 days. Hypertonic solutions Providing the patient is normocapnic and adequately sedated, hypertoni c solutions are the \201 rst-line agents used to treat persistently elevated ICP. Promisi ng level 3 evi- dence is emerging on the use of hypertonic saline, and this may provide a u seful treatment in the future. Boluses of 2ml/kg of a 20% mannitol solution provide rapid a nd effective reduction in ICP. Metabolic monitoring Focal tissue oxygenation (PBRO2) Continuous measurement of tissue oxyg enation is available and in current use in some departments in the UK. PBrO2 gives an early warning of impending ischaemia and may allow for less vigorous treatment of ICP. It also c an guide alternative therapies to improve oxygen delivery, such as red cell transfusion and inotropes. A limitation is that oxygenation in a single area of brain tissue may not re \202 ect other areas of the brain, and that \200\230tissue ischaemia \200\231 may be due t o mitochondrial failure. There is some evidence that directing treatment to PBrO2 improves outcome in com- parison with ICP-directed treatment. Jugular bulb oxygen saturation (SjvO2) SjvO2 is a global measure of brain oxygenation; however, it suffers from the same limitati ons as PBrO2 in that areas of the brain that are not extracting oxygen will falsely elevate readings. Metabolic suppression Suppression of cerebral electrical activity produces signi \201 - ca nt reductions in ICP in patients who have intact coupling between cerebral metabolism and \202 ow. This can be tested by PaCO2 responsiveness or a test dose of hypnotic agent. In r esistant raised ICP, barbiturates are recommended. These are administered as boluses follow ed by an infusion, with continuous monitoring of brain electrical activity to achieve burst suppression. Surgical intervention Early surgical intervention saves lives after head injury. Indication s include hydrocephalus, contusions, extradural and subdural haematomas. In addition, the r ole of decompressive craniectomy is currently under investigation, with some promising pilo t studies. Cerebral blood \202 ow PET scanning, perfusion CT scans and perfusion-weighted MRI techni ques have all been used to estimate CBF. These techniques are not continuous, are technical ly dif \201 cult and are unable to predict what level of perfusion is required to match me tabolic demands for individual areas of the brain. They are, however, useful as research to ols. Cerebral protection Hypothermia Pyrexia is common in brain injury and is associated with a worsening of outcome. It may be centrally mediated and independent of an infective cause. H ypothermia has been shown to be effective in animal models; however, trials of therapeutic hypothermia have failed to show bene \201 t. Hypothermia is associated with an increase in need for support of the circulation, electrolyte abnormalities, a raised serum amylase, bl eeding and arrhythmias. Maintenance of normothermia is common practice either by active coo ling or by pharmacological intervention. The lack of evidence surrounding pharmacological n euro- protective intervention makes it unlikely that changes in care for patients with seve re head injury in hospitals without neurological services would deliver outcome improvement s of the magnitude that could follow signi \201 - cant expansion in neurological intensive care facilities. Microdialysis Future monitors may include microdialysis of glucose, pyruvate and lactate, i ndicating areas of brain with inade- quate perfusion. Measurement of excitotoxic amines and in \202 ammatory mediators may also be useful in the future; but this is still at the exp erimental stage. General ICU care The focus of care is the avoidance of medical complications and the provis ion of an environment optimal for brain recovery. The Brain Trauma Foundation (BTF) recomme nds; \200 Keep sodium >140mmol/l. A decrease in serum sodium produces an osmotic gradient across the blood \200\223 brain barrier and aggravates cerebral oedema. Avoid hyperglycaem ia (treat blood glucose >11mmol/l). Hyperglycaemia may aggravate ischaemic brain injury by increasing cerebral lactic acidosis. Feed via orogastric tube and use motility agents as re quired Use TED stockings and avoid low dose heparin Apply 15 \200\22330 head-up tilt with head in neutral position No parenteral, non-ionic \202 uid to be given. Conclusion It therefore remains the priority of neurointensive care to deliver the assured physiological parameters and prevent medical and surgical complications impairing the patie nt \200\231s recovery. \200 Further reading http://www2.braintrauma.org/site/Pageserver? pagename=guidelines Speci \201 c treatment of raised ICP Hyperventilation Prolonged hyperventilation is detrim ental; however, there is controversy whether short-term hyperventilation in response to an acute rise in ICP is harmful. It is ef \201 cacious in reducing ICP; but there is doubt as to how quickly after hyperventilation CBF returns to normal, which may be up to 24h. The B TF guidelines recommend that hyperventila- tion is limited to short periods and only when r esponse to other medical treatments for raised ICP have failed. Recommended target PaCO2 is between 4 and 4.5kPa. Marshall LF. Epidemiology and cost of central nervous system injury. Clin Neurosurg 2000; 46: 105 \200\22312. Ravussin P. Abou-Madi M, Archer D, et al. Changes in CSF pressure after mannitol in patient s with and without elevated CSF pressure. J Neurosurg 1988; 69: 869 \200\22376. Stieffel MF, Spiotta A, Gracias V, et al. Reduced mortality rate in patients with severe tr aumatic brain injury treated with brain tis- sue oxygen monitoring. J Neurosurg 2005; 103: 805 \200\22311. Sahuquillo J, Arikan F. Decompressive craniectomy for the treat- ment of refractory high in tracranial pressure in traumatic brain injury. Cochrane Database Syst Rev 2006; (4): CD0039 83. 486 B WINTER, S SARKAR & H PATTANI Spinal trauma with marked physiological sequelae, which are dependent on the level and extent of injury. Acutely there is a \202 accid paralysis below the spinal level, which after resolution of the spinal shock phase develops into spasticity. Respiratory failure is more common in com plete than incomplete SCI. Diaphragmatic supply is from C3 \200\2235, and injury above C3 r esults in apnoea. Injuries below C5 may have diaphragmatic function maintained. However, ma rked ventilatory dysfunction is apparent in the acute setting, with loss of intercostal mus cle function; diaphragmatic con- traction and descent occurs with chest wall indrawing rath er than expansion. FVC and maximal inspiratory force are reduced by nearly 70%. Similarly, loss of abdominal wall contraction reduces expiratory effort. These result in atel- ectasis , hypoventilation and hypoxaemia. Ventilator dependence correlates strongly with level of i njury; C1 \200\2234: 65 days, C5 \200\2238: 22 days, thoracic: 12 days. One-third of patien ts with cervical injuries will require intubation within the \201 rst 24h of injury. Spec i \201 c indications include: \200 fatigue \200 VC <1l \200 rising PaCO2 \200 risi ng respiratory rate