PT >100, INR >6.5. Creatinine >200 mol/L. Grade 3 \200\2234 encephalopathy. PARACETAMOL POISONING 525 1.4 1.2 1 ) l / l o m m Treatment with N-acetylcysteine required 0.8 ( l e v e l l o m a t e c a r a P 0.6 Treatment with N-acetylcysteine required for high risk patients 0.4 0.2 Treatment with N-acetylcysteine not required 0 4 6 8 10 12 14 16 18 20 22 24 Time since ingestion (h) Fig. 30.1. Graph for predicting treatment requirement. Treatment is required at lower levels if the patient is a known alcoholic, protein-depleted , HIV-positive, or is taking enzyme-inducing drugs, e.g. phenytoin. See also: Liver function tests, p218; Coagulation monitoring, p222; Toxicology, p228; Acute liver failure, p430; Poisoning \200\224general principles, p520. 526 CHAPTER 30 Poisoning Sedative poisoning Patients can present with alterated consciousness, respiratory failure, and sometimes, cardiovascular disturbance. Treatment is usually supportive. Consider the po ssibility of rhabdomyolysis after prolonged immobility. Benzodiazepine poisoning \200 Benzodiazepines are common agents used for self-poisoning, but severe features are uncommon , except at extremes of age. Flumazenil may be used as a speci \201 c antidote (0.2 \200 \2231.0mg IV given in 0.1mg increments), but is dangerous in benzodiazepine dependence and mixed poisoning with tricyclic antidepressants. Flumazenil is short-acting so benzodiazepin e reversal may be temporary. Rapid reversal of benzodiazepines may lead to anxiety attacks or seizures. Opioid poisoning \200 Treatment is supportive with attention particularly to respiratory depression and cardiovas cular disturbance. Naloxone may be used as an antidote (0.2 \200\2230.4mg IV) although rapi d reversal is not desired in opioid abusers. Naloxone is short-acting so reversal may be te mporary. Consider HIV or other viral infection, and endocarditis in IV drug abusers. In iat rogenic poisoning, naloxone will reverse the pain relief that opioids were given for. In th ese cases, respiratory depression is better reversed by the non-speci \201 c respiratory s timulant, doxapram (1.0 \200\223 1.5mg/kg over 30s IV followed by 1.5 \200\2234.0mg/min). \200 Barbiturates Treatment is supportive with particular attention to respiratory and car- diov ascular depression. Vasodilatation may be extreme requiring \202 uid support and, in some cases, inotropic support. Phenobarbital may be eliminated by forced alkaline diuresis. SEDATIVE POISONING 527 See also: Airway maintenance, p40; Respiratory stimulants, p256; Coma, p438; Poisoning \200 \224general principles, p520. 528 CHAPTER 30 Poisoning Tricyclic antidepressant poisoning Tricyclic antidepressants are prescribed to patients who are at greatest risk of a suicide attempt. They are rapidly absorbed from the gastrointes- tinal tract although gastric emptying is delayed. Clinical features \200 \200 Anticholinergic effects (dilated pupils, dry mouth, ileus, urine retention). Arrhythmias (o ften associated with prolonged QT interval and broad QRS complex). Hypotension related to a rrhythmias and/or cardiac depression through Na+ channel blockade. Hyper-re \202 exia with extensor plantars, visual hallucinations, coma, and seizures. Drug levels do not correlate with severity. Metabolic acidosis in severe poisoning. Metabolism is usually rapid and imp rovement is usually within 24h. \200 Management 1. There is no speci \201 c treatment for tricyclic antidepressant poisoning. 2 . Patients require ECG monitoring during the \201 rst 24h and until ECG changes have disappeared for 12h. 3. Activated charcoal (50g) via a nasogastric tube will adsorb tricyclics remaining in the bowel. 4. Cardiac arrhythmias are more common if there is an acidosis. Give bi- carbonate to achie ve an arterial pH of 7.5. If arrhythmias occur with no acidosis and fail to respond to trea tment with amiodarone or pheny- toin, bicarbonate (25 \200\22350mL 8.4% IV) may still be us eful. 5. Seizures are best managed with benzodiazepines and phenytoin. TRICYCLIC ANTIDEPRESSANT POISONING 529 See also: Airway maintenance, p40; Sodium bicarbonate, p244; Tachyarrhythmias, p384; Coma, p438; Generalized seizures, p444; Poisoning \200\224general principles, p520. 530 CHAPTER 30 Poisoning Amphetamines and Ecstasy Amphetamines, e.g. 3,4-methylenedioxymethamphetamine (MDMA, \200 \230Ecstasy \200\231) and 3,4-methylenedioxyethamphetamine ( \200\230Eve \200\231), are sti mulants taken pre- dominantly for recreational use or as appetite suppressants. They are ha llucinogenic at higher doses. MDMA cause rapid decreases in central nervous system 5-hydrox ytryptamine and 5-hydroxyindole-3-acetic acid levels and increases in dopamine release. Clinical features of overdose \200 Agitation, hyperactivity, hypertension, hallucinations, paranoia followed by exhaustion, co ma, convulsions, and hyperthermia. Idiosyncratic responses to Ecstasy and Eve are more comm on with numerous reports of mortality and major morbidity following ingestion of just 1 \200\2232 tablets. Ingestion in hot environments, e.g. nightclubs, and concurrent dehydrati on is more likely to be associated with idiosyncratic responses. Features include profound hyperthermia (>40*C), agitation, seizures, muscle rigidity, hypertension, tachycardia, swea ting, coma, disseminated intravascular coagulation, and rhabdomyolysis. These complications lead to hypovolaemia, electrolyte imbalance (particularly hyperkalaemia), and a metabolic acidosis. Some patients taking Ecstasy or Eve have been admitted with water intoxication an d acute hyponatraemia following ingestion of large amounts of water. Management 1. Supportive care, including airway protection, \202 uid resuscitation, elec- trolyte correction, and if needed, mechanical ventilation. 2. Early stages of amphetamine poisoning can be often controlled with tepid sponging, chlor promazine, B-blockade. Forced acid diuresis to increase urinary excretion is rarely needed. 3. Manage severe complications as they arise, e.g. rapid cooling for hyper- pyrexia, antico nvulsants for seizures, urine alkalinisation 9 fasciotomies for rhabdomyolysis, platelet, a nd fresh frozen plasma infusions for co- agulopathy. 4. Dantrolene is sometimes given to treat hyperpyrexia at a dose of 1mg/ kg IV, repeated to a cumulative maximum dose of 10mg/kg, particularly if the temperature is >40*C. However, n o outcome bene \201 t has been reported through its use and it can cause side effects. AMPHETAMINES AND ECSTASY 531 See also: Airway maintenance, p40; Hypertension, p382; Coma, p438; Delirium, p442; Generali zed seizures, p444; Hyperkalaemia, p488; Metabolic acidosis, p502; Poisoning \200\224genera l principles, p520; Hyperthermia, p600; Rhabdomyolysis, p612. 532 CHAPTER 30 Poisoning Cocaine poisoning Modes of action \200 Blocks reuptake of dopamine (causing euphoria, hyperactivity) and norepinephrine (causing v asoconstriction and hypertension). Arrhythmias may also result. Blocks Na+ channels, result ing in a local anesthetic action and myocardial depression. Platelet activation. Mitochondr ial dysfunction leading to myocardial depression. \200 Complications \200 Chest pain related to myocardial ischaemia or infarction, or to coronary artery spasm. Hear t failure. Seizures. Cerebrovascular accidents. Pneumothorax. Rhabdomyolysis. Premature lab or \200\224abruption. Agitated delirium, hyperthermia. \200 \200 \200 \200 \200 \200 Management 1. Local chest pain guidelines should be followed. ECG abnormalities of- ten res olve within 12h. Arrhythmias should be treated conventionally, but avoiding B-blockers (lea ving an unopposed A-action). 2. Verapamil or phentolamine may be useful for treating hypertension. 3. Oxygen. 4. Give be nzodiazepine for agitation, delirium, chest pain. 5. Aspirin for chest pain, CVA. 6. Nitrat es for chest pain. 7. Low molecular weight heparin or clopidogrel may also be given unless the blood pressure is very high. 8. Urinary alkalinisation for rhabdomyolysis. COCAINE POISONING 533 See also: Pneumothorax, p368; Hypertension, p382; Acute coronary syndrome (1), p388; Acute coronary syndrome (2), p390; Heart failure \200\224assessment, p392; Heart failure \200\224 management, p394; Delirium, p442; Generalized seizures, p444; Stroke, p452; Poisoning \200 \224general principles, p520; Hyperthermia, p600; Rhabdomyolysis, p612. 534 CHAPTER 30 Poisoning Inhaled poisons Carbon monoxide (CO) CO poisoning should be considered in anyone found in a smoke- \201 lled, enclosed space. CO displaces oxygen from hemoglobin to which it has 200 times greater af \201 nity and thus prevents oxygen carriage. There is also a direct toxi c effect on mitochondrial oxidative phosphorylation as it com- petes with oxygen for the sa me binding site on cytochrome oxidase. Clinical features \200 Fatigue, headache, vomiting, dizziness, confusion, dyspnoea, cerebral oedema in severe pois oning. A cherry red appearance of the skin and mucosae are classical. PaO2 will be normal u nless there is respiratory depression and pulse oximetry is misleading. The half-life of ca rboxyhaemoglobin is 4h when breathing room air and 50min when breathing 100% oxygen. \200 Management \200 Carboxyhaemoglobin levels should be measured by a co-oximeter and treatment started immedia tely with oxygen at the maximum concentration that can be delivered (ideally FIO2 1.0). If carboxyhaemoglobin levels >25% or there is associated mental disturbance, the optimal treat ment is hyperbaric oxygen at 3 atmospheres for 30min, repeated 6-hourly if levels remain >2 5%. Death is likely with carboxyhaemoglobin levels >60%. High concentration oxygen treatmen t should continue until carboxyhaemoglobin levels <10%. Cyanide \200 Severe cyanide poisoning has an extremely rapid onset and occurs in some cases of smoke inh alation. Survival may be associated with anoxic brain damage. Diagnosis must be made clinic ally; cyanide levels take >3h to perform. Clinical features Clinical features include anxiety, agitation, hyperventilation, headache, loss of consciousness, dyspnoea, weakness, dizziness, and vomiting. The skin remains pink and hypotension may be severe. An unexplained metabolic acidosis is suggestive. Management \200 High concentration oxygen should be given, but is only truly effective when given at hyperb aric pressures. In mild cases, rapid, natural detoxi \201 cation reduces cyanide levels by 50% within 1h, allowing supportive therapy only. Sodium thiosulphate (150mg/kg IV followed by 30 \200\22360mg/kg/h) converts cyanide to thiocyanate and should be used if there is un consciousness. However, it is slow-acting. Nitrites produce methaemoglobinaemia (metHb) and may potentially worsen cyanide toxicity. Dicobalt edetate (300mg IV), the speci \201 c an tidote is toxic (vomiting, urticaria, tachycardia, hypotension, dyspnoea, chest pain) in th e absence of cyanide. It is best avoided unless cyanide toxicity is likely. INHALED POISONS 535 Key paper Weaver LK, Hopkins RO, Chan KJ, et al. (2002) Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med 347: 1057 \200\22367. See also: Oxygen therapy, p38; Blood gas analysis, p154; Poisoning \200\224general principl es, p520. 536 CHAPTER 30 Poisoning Household chemicals Corrosives Strong acids and alkalis are increasingly available in the h ousehold and ingestion may lead to shock and bowel perforation. Avoid gastric elimi- nation techniques since aspiration of corrosives may cause severe lung damage. Early surgical rep air of perforation may be necessary. Petroleum Access to petroleum in the home is easy. Clinical features Gut ingestion and absorption gives clinical features similar to those of alcohol intoxication with more severe neurological depression. Management \200 Avoid gastric elimination techniques since a few drops of petroleum spilling into the lungs can lead to a severe pneumonitis. This is due to the low surface tension and vapor pressur e of petroleum allowing rapid spread through the lungs. Treatment involves supportive thera py and 250mL liquid paraf \201 n orally. Paraquat Paraquat is widely available as a selective weedkiller which is inactivated on con tact with the soil. A dose of 2 \200\2233g is usually fatal (equivalent to 80 \200\223 120g of granules or 10 \200\22315mL of industrial liquid concentrate). It inhibits mitochondria and generates superoxide which damages lipid membranes. Clinical features \200 Very little of the ingested paraquat is absorbed from the gut, but a large dose will lead r apidly to shock with widespread tissue necrosis. A burning sensation in the mouth and abdom en, development of painful mouth ulcers and, after several days, a relentless, proliferativ e alveolitis leading to ARDS and death from pulmonary \201 brosis. Liver, heart, and kidn ey may also be affected. Death may be slow and take up to 30 days following ingestion. Management \200 Treatment should begin on clinical grounds in view of the severity of toxicity and the time taken for laboratory con \201 rmation. Remove patient from ongoing contact, decontaminate skin with large volumes of water, and remove their clothing. Staff should take care not to contaminate themselves. Urgently instill 1000mL water containing 150g Fuller \200\231s ear th via a nasogastric tube. Alternatively, 1g activated charcoal may be given. A cathartic s uch as 25g magnesium sulfate should be given. Severe diarrhea may ensue, requiring careful \202 uid management. If paraquat poisoning is con \201 rmed, 200 \200\223500mL of 30% Fu ller \200\231s earth is given 2-hourly for 24h via a nasogastric tube. Fluid repletion to e ncourage renal excretion. Pulmonary \201 brosis is more severe when breathing high FIO2. Oxygen should be avoided but, in severe hypoxaemia, give the lowest concentration possible accepting low PaO2. Liposomal superoxide dismutase and glutathione peroxidase are used expe rimentally. \200 \200 \200 HOUSEHOLD CHEMICALS 537 See also: Poisoning \200\224general principles, p520. 538 CHAPTER 30 Poisoning Methanol and ethylene glycol Methanol Toxicity mainly due to oxidation of methanol to formi c acid and formal- dehyde. The oxidative pathway is an enzymatic process involving alcohol dehydrogenase, but proceeds at 20% of the rate of ethanol oxidation. Clinical features Clinical features of poisoning include blindness (due to concentration of methanol in the vitreous humor), severe metabolic acidosis, headache, nausea, vomiting, an d abdominal pain. Management \200 Metabolism of methanol is slow so treatment will need to be prolonged (several days). Treat ment includes ethanol or, preferably, fomepizole, to inhibit alcohol dehydrogenase. On pres entation 1mL/kg ethanol (50%) can given orally followed by 0.5mL/kg 2-hourly for 5 days. Al ternatively, an infusion can be given (7.5mL/kg ethanol (10%) over 30min followed by 0.5 \200\2231.0mL/kg/h aiming for blood ethanol levels of 100 \200\223150mg/dL). Levels need to be repeated frequently to avoid under- or overdosing. Block metabolism with 4-methyl pyraz ole (fomepizole) infused or injected 12-hourly IV. Though more expensive than alcohol, it i s effective, well-tolerated, and there is no need for therapeutic monitoring. If methanol l evels are >1000mg/L, haemodialysis is used until levels are <250mg/L. Ethylene glycol Ethylene glycol is partially metabolized by alcohol dehydrogenase to oxalic acid which is responsible for a severe metabolic acidosis, renal failure, and seizures. Clinical features Clinical suspicion is aroused by odorless drunkenness, oxalate crystals i n the urine or blood, and the severe acidosis. As little as 50mL can be fatal. Management Treatment is as for methanol. METHANOL AND ETHYLENE GLYCOL 539 See also: Blood gas analysis, p154; Metabolic acidosis, p502; Poisoning \200\224general pri nciples, p520. 540 CHAPTER 30 Poisoning Organophosphate poisoning Organophosphates in pesticides are the major cause of suicidal po isoning in developing countries and are used as nerve agents in terrorist attacks (e.g. Sar in, Tabun, VX, GF). They can be absorbed through intact skin, gut, or inhaled. Their mode o f toxicity is via inhibiting cholinesterase. Cholinergic (anticholinesterase) syndrome \200 \200 \200 \200 \200 \200 \200 \200 \200 Salivation, lacrimation, bronchorrhoea, sweating. Anxiety and restlessness. Vomiting, diarr hea. Bradycardia. Bronchospasm. Pulmonary oedema. Miosis. Hyperglycaemia. Muscle weakness a nd fasciculation with paralysis. Management \200 Skin decontamination should never be neglected or hurried but must occur prior to critical care admission. The patient \200\231s clothes should be removed. The patient \200\231s body should then be thoroughly washed with soap and water to prevent further absorption from th e skin. Staff should be protected from the organophosphate by wearing gloves, gowns, and ey e protectors. The airway should be protected and oxygen given to avoid hypoxaemia (ventricu lar \201 brillation more common with atropine in hypoxaemia). Atropine \200\224antagonize s acetylcholine at muscarinic receptors. A dose of 2mg should be given every 5 \200\22310 m inutes until the mouth is dry. Severe poisoning may require >100mg atropine. Pralidoxime \200\224reactivates inhibited enzymes if given before the agent permanently binds to the en zyme. A dose of 30mg/kg, repeated every 4 \200\2236 hours or an infusion of 8mg/kg/h to a m aximum dose of 12g in 24 hours should be given. Diazepam \200\224neuroprotection. ORGANOPHOSPHATE POISONING 541 See also: Bronchodilators, p254; Chronotropes, p274; Bradyarrhythmias, p386; Poisoning \200 \224general principles, p520. This page intentionally left blank 543 Chapter 31 Infection and in \202 ammation Infection control \200\224general principles 544 Infection control \200\224HIV 546 Infectio n control \200\224dangerous pathogens 548 Routine changes of disposables 550 Infection \200 \224diagnosis 552 Infection \200\224treatment 554 Systemic in \202 ammation/multi-organ fa ilure \200\224causes 556 Systemic in \202 ammation/multi-organ failure \200\224management 558 Sepsis and septic shock \200\224treatment 560 Multi-resistant infections 562 Necrotisin g fasciitis 564 HIV-related disease 566 Malaria 568 SARS, VHF, and H5N1 570 Rheumatic disor ders 572 Vasculitis 574 Toxic epidermal necrolysis 576 Anaphylactoid reactions 578 544 CHAPTER 31 Infection and in \202 ammation Infection control \200\224general principles Nosocomial infection is a major cause of morta lity, morbidity, and increased length of stay. Marked variations in infection control polic ies for isolation, microbiological surveillance, handwashing, glove and gown use, impregnat ed vascular catheter use, duration of indwelling catheters, and frequency of change of disp osables re \202 ect a weak evidence base. It is generally accepted that handwashing before and after patient contact and strict aseptic technique when performing procedures are mand atory. Staff measures (universal precautions) The authors currently use the following precautions: \200 Remove watches and jewelry, remove long-sleeved white coats and jackets, roll shirt sleeves up to elbow. Hand and forearm washing before and after touching patient. Use alcohol-based gel after skin contact, but soap and water for body \202 uid contact or if patient has C . dif \201 cile (alcohol does not eradicate spores). Wear disposable aprons and gloves if in contact with patient. Wear gloves and aprons when handling any body \202 uid and eye p rotection when there is any danger of \202 uid or droplet splash. Use strict aseptic tech nique for invasive procedures (e.g. central venous catheter insertion) and clean technique for basic procedures, e.g. endotracheal suction, changing ventilator circuits, or drug infu sions. Bedside equipment (including computer keyboards, infusion and syringe pumps, ventila tors, and bed rails) should be cleaned regularly. Previous immunization against hepatitis B , tuberculosis. Stethoscopes should be cleaned between patients. Clear signposting of preca utions to be taken on access doors. \200 \200 \200 Visitors \200 Non-ICU medical and paramedical staff, relatives, and friends should adhere to the policies in force, e.g. handwashing, aprons, and gloves. Traf \201 c through the ICU should be min imized. Cross-infection \200 Inform the Infection Control team should cross-infection arise. It may be worthwhile typing the microorganism to con \201 rm an outbreak. Source isolate the patient for multi-resist ant or virulent organisms. If cross-infection persists/spreads, other sources should be sou ght, e.g. taps, sinks, reusable equipment (rebreathing bags, ventilators). \200 Isolation \200 Source isolation \200\224for patients carrying potentially contagious, virulent or multires istant organisms, e.g. tuberculosis. Protective isolation \200\224for immunosuppressed pati ents at risk of acquiring infection, e.g. when neutropaenic following chemotherapy Microbiological surveillance Policies vary; some routinely screen sputum, bronchoalveolar l avage, blood, urine, and drain \202 uid every 2 \200\2234 days while others screen only o n clinical indication, e.g. deteriorating gas exchange, pyrexia, neutrophilia. Some perform routine MRSA surveillance of hairline 9 nose 9 groin with rapid PCR-based technologies whe re results are available within 6h. INFECTION CONTROL \200\224GENERAL PRINCIPLES 545 See also: Critical Care Unit layout, p2; Patient safety, p14; Bacteriology, p224; Virology, serology, and assays, p226; Infection control \200\224dangerous pathogens, p548; Routine c hanges of disposables, p550; Infection \200\224 diagnosis, p552; Neutropaenia and infection , p628. 546 CHAPTER 31 Infection and in \202 ammation Infection control \200\224HIV Protection of staff from transmission of HIV follows standard universal precautions: \200 \200 \200 \200 Do not handle body \202 uids without gloves. Protect face and eyes where there is a risk of splash contamination. Dispose of needles in appropriate burn bins without re-sheathing. Clean up any \202 uid spillages immediately. Robust procedures are usually adhered to when a patient is known to be HIV-positive; the re al risk is in the patient of unknown HIV status. Patients presenting to critical care with non-HIV-related illness may also be unknown positives. It follows that precautions should b e taken for all patients. Staff exposure Needlestick injury, eye or skin cut contact with the patient \200\231s bodil y \202 uids should be prevented by strict infection control procedures. However, should e xposure happen, wash the area thoroughly and contact the desig- nated person within the hos pital promptly (e.g. HIV specialist, microbiol- ogist) who can advise on risk and the desir ability of taking post-exposure anti-retroviral prophylaxis (typically two nucleoside rever se transcriptase inhibitors for four weeks). The chance of getting infected from a needle- stick injury is <1 in 300. Different countries have different policies with regard to testing HIV status on incapacita ted patients whose blood or other bodily \202 uid has been in contact with a health care worker. Current UK General Medical Council policy has recently changed to not allow testing in such cases. INFECTION CONTROL \200\224HIV 547 See also: Critical Care Unit layout, p2; Patient safety, p14; Infection control \200\224gen eral principles, p544; Multi-resistant infections, p562; SARS, VHF, and H5N1, p570. 548 CHAPTER 31 Infection and in \202 ammation Infection control \200\224dangerous pathogens Risk assessment Before exposing staff to pati ents with dangerous pathogens, there must be a full assessment of the risks. Advice should be sought from communicable disease experts. This must include access to intelligence relat ing to likely pathogens in endemic areas visited or, if locally acquired, local infection s urveillance data. Ideally, a risk assessment will have been performed in advance of the ref erral and should include: \200 \200 \200 \200 Which pathogen may be present (hazard identi \201 cation). The likelihood of infection. Th e severity of infection if it occurs. Where the pathogen is likely to be present (e.g. in b lood samples or spillages, on contaminated instruments and equipment, in waste, and on cont aminated clothing). Ways in which staff may be exposed (e.g. through direct personal exposu re to blood in invasive procedures, accidental exposure, handling contaminated items for cl eaning or disposal). Estimate of exposure, i.e. number and range of sources and frequency o f contact, taking account of systems of work and protective measures Control measures \200 \200 Universal precautions. Airborne precautions (negative pressure isolation room and use of \201 lter respirators conforming to European Standard EN 149:2001 or equivalent for people entering the room). Contact precautions (long-sleeved, \202 uid-repellent gown, and prote ctive gloves with tight- \201 tting cuffs. In addition, there should be eye protection for organisms that can infect via eye splash). Clinical waste precautions (in addition to univ ersal precautions for handling waste, leak-proof biohazard bags must be used for safe dispo sal). INFECTION CONTROL \200\224DANGEROUS PATHOGENS 549 See also: Patient safety, p14; Infection control \200\224general principles, p544; Infectio n control \200\224dangerous pathogens, p548; HIV-related disease, p566. 550 CHAPTER 31 Infection and in \202 ammation Routine changes of disposables Care of intravascular catheters \200 Sites should be covered with transparent semi-permeable dressings to allow observation and prevent secretions from accumulating. Routine changes of intravascular catheters are no lon ger recommended. As the risk of infection increases considerably after a week in situ, cath eters should be removed as soon as clinically feasible. Catheters should be changed to a fr esh site if: \200 \200 \200 The old site appears infected. The patient shows signs of severe infection. A positive grow th is obtained from a blood culture drawn through the catheter or from the tip of the previ ous catheter. Catheter changes over a guidewire are no longer recommended as sterility cannot be assured. This can be considered if new central venous access if dif \201 cult or the risk of inser tion is high (e.g. coagulopathy). Routine changes of disposables Frequency Ventilator circuit with bacterial \201 lters Between patients unless soiled Ventilator circuit with water bath humidi \201 er Daily Endotracheal tube catheter mount and bacterial \201 lter Between patients unless soiled Oxygen masks Between patients unless soiled CPAP circuits Between patients unless soiled Rebreathing bags and masks Between patients unless soiled Intravenous infusion giving sets 48h Parenteral nutrition giving sets Daily Enteral feeding giving sets Daily Arterial/venous pressure transducer sets 48h Urinary catheter bags Weekly ROUTINE CHANGES OF DISPOSABLES 551 See also: Arterial cannulation, p166; Central venous catheter \200\224insertion, p168; Infe ction control \200\224general principles, p544. 552 CHAPTER 31 Infection and in \202 ammation Infection \200\224diagnosis Infection is a common cause of critical care admission and the major secondary complication. Critically ill patients are predisposed to further infection as many of their natural barriers and defense mechanisms are lost, altered, or penetrated. They are often heavily instrumented, sedated, and immobile. They often develop immune hypor esponsiveness as part of their critical disease process, notwithstanding any therapeutic im mune suppression they may have received. The high antibiotic load encourages colonization b y pathogenic organisms and subsequent development of infections by multidrug resistant and/ or atypical (e.g. fungi) organisms. Sepsis is de \201 ned as the systemic in \202 ammatory response to an infectious insult ( either con \201 rmed or highly likely). Whereas infection is a localized phenomenon, the s eptic process often affects distant organs. Diagnosis \200 Often problematic in the critically ill patient as focal signs may be lacking and/or camou \202 aged by concurrent disease (e.g. ventilator-associated pneumonia on top of ARDS). Sym ptoms are often not upcoming due to the patient \200\231s state of mental incompetence. In addition, all of the traditional clinical and biochemical markers of infection are non-spec i \201 c. These include pyrexia, neutrophilia, and altered sputum. Furthermore, the freque nt presence of colonizing organisms e.g. MRSA on skin, Pseudomonas aeruginosa in the respir atory tract, does not imply concomitant infection. As a consequence, many patients are over treated with antibiotics, enhancing the risk of overgrowth of resistant/atypical organisms. Markers of in \202 ammation (C-reactive protein, procalcitonin) may be useful, though stu dies have produced con \202 icting results as to their speci \201 city/sensitivity in dia gnosing underlying infection/sepsis. The value of routine screening (microbiological survei llance) is not proven though this may help to identify infecting organisms earlier. For cas es of suspected infection, appropriate samples should be taken for analysis, including bloo d, sputum, wound swabs, drainage \202 uid, aspirated pus, catheter tips, cerebrospinal \202 uid, etc. These should generally be taken before new antibiotics are commenced. Consid er less common causes of infection such as endocarditis or osteomyelitis, particularly if t he patient fails to settle after a standard course of therapy. Differential diagnosis of pyrexia \200 \200 Infection. Non-infective causes of in \202 ammation, e.g. trauma, surgery, burns, myocardi al infarction, vasculitis, hepatitis, cholecystitis, pancreatitis. Adverse drug reactions. Excessive ambient heating. Miscellaneous causes, e.g. neoplasm. \200 \200 INFECTION \200\224DIAGNOSIS 553 De \201 nitions Infection Microbial phenomenon characterized by an in \202 ammatory respo nse to the presence of microorganisms or the invasion of normally sterile host tissue by th ose organisms. Bacteraemia The presence of viable bacteria in the blood. Sepsis The systemic response to infection. De \201 nition as for systemic in \202 amma- t ory response syndrome (SIRS) but as a result of infection. SIRS Two or more of: \200 \200 \200 \200 Temperature >38*C or <36*C. Heart rate >90bpm. Respiratory rate >20 breaths/min or PaCO2 <3 2mmHg (4.3kPa). WBC >12,000cells/mm3, <4000/mm3, or >10% immature forms. Sites of infection pre- and post-admission to critical care Secondary site of infection acquired while in Critical Care Organ Primary site of infection needing admission to Critical Care Brain + + Sinuses \200\223 + Cannula/wound sites ++ +++++ Other skin and soft tissue ++ + Chest ++++ ++++ Urogenital tract ++ + Abdomen ++++ ++ Bone + + Heart valves + + Key paper American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference. (1992) De \201 nitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20: 864 \200\22374. See also: Bacteriology, p224; Virology, serology, and assays, p226; Acute chest infection ( 1), p356; Acute chest infection (2), p358; Systemic in \202 ammation/multi-organ failure \200\224causes, p556; Pyrexia \200\224causes, p602; Pyrexia \200\224management, p604. 554 CHAPTER 31 Infection and in \202 ammation Infection \200\224treatment Principles \200 Drain pus. \200 Change cannula sites, if ne cessary. \200 Appropriate antibiotic therapy after laboratory specimens taken \200\224may not be necessary for mild infections where cause has been removed, e.g. an infected cathet er. Radiological and/or surgical intervention, if indicated. Antimicrobials Regular input from microbiology 9 infectious disease specialists is rec- omm ended to advise on best options for empirical therapy and for pos- sible modi \201 cation based on early communication of laboratory results (including antibiotic sensitivity patter ns). Empirical antimicrobial therapy is guided on illness severity, the likely site of infection and infecting organism(s), whether the infection is com- munity-acquired or nosocomial (in cluding Critical Care acquired), immu- nosuppression status, and known antibiotic resistanc e patterns of hospital and local community organisms. In general, critically ill patients should receive parenteral antibiotics at appropriate do sage, taking into account any impaired hepatic or renal clearance or concurrent renal repla cement therapy. Broad-spectrum therapy may be initially needed, with re \201 nement, cessa tion, or change after 2 \200\2233 days, depending on clinical response and sensitivity patt erns of organisms subsequently isolated. The duration of treatment remains highly contentio us. Apart from speci \201 c conditions such as endocarditis, tuber- culosis, and meningiti s where prolonged therapy is probably advisable, it may be suf \201 cient to stop within 3 \200\2235 days provided the patient has shown adequate signs of recovery. Patients not responding or deteriorating should be considered as either treatment failures or inappropriately treated (i.e. no infection was present in the \201 rst place). Commonl y accepted markers of infection are not speci \201 c in the critically ill patient. Indeed , pyrexia may settle on stopping antibiotic treatment. Cessation or change of antibiotic th erapy must be considered on individual merits according to the patient \200\231s condition and any subsequent laboratory results. An advantage of ceasing therapy is the ability to ta ke further specimens for culture in an antibiotic-free environ- ment. Other measures It may be necessary to remove indwelling pacemakers, tunneled vascular cathe ters, prosthetic joints, plates, implants, grafts, and stents if these are the suspected ca use of infection. This should be done in consultation with microbiologists and the appropri ate specialist as individual risk and bene \201 t need to be carefully weighed up. INFECTION \200\224TREATMENT 555 Specimen antibiotic regimens (organism unknown) 2nd/3rd generation cephalosporin OR quinolone OR carbapenem OR piptazobactam 9 Aminoglycosi de (if Gram-negative suspected) 9 Metronidazole (anaerobic cover) 9 Glycopeptide or linezol id (if MRSA suspected) 2nd/3rd generation cephalosporin + macrolide Sepsis of unknown origin Pneumonia \200\224 community-acquired 3rd generation cephalosporin OR quinolone OR carbapenem OR piptazobactam 9 aminoglycoside ( if Gram-negative suspected) + Teicoplanin, vancomycin + rifampicin or linezolid (if MRSA li kely) Pneumonia \200\224 nosocomial Skin and soft tissue Flucloxacillin (if MSSA likely) Glycopeptide or linezolid (if MRSA likely) Benzylpenicillin or clindamycin (if Streptococcus suspected) 2nd/3rd generation cephalosporin OR quinolone OR carbapenem OR piptazobactam 9 Aminoglycoside 9 metronidazole 2nd/3rd generation cephalos porin OR quinolone OR carbapenem OR piptazobactam 9 Aminoglycoside + Metronidazole 2nd/3rd generation cephalosporin OR quinolone OR carbapenem OR piptazobactam 9 Aminoglycoside Abdominal Gynecological Nephro-urological NB. Local resistance patterns should be borne in mind when prescribing. See also: Antimicrobials, p326; Acute chest infection (1), p356; Abdominal sepsis, p422; Me ningitis, p446; Tetanus, p462; Botulism, p464; Sepsis and septic shock \200\224treatment, p 560; Multi-resistant infections, p562; HIV-related disease, p566; Malaria, p568; SARS, VHF, and H5N1, p570. 556 CHAPTER 31 Infection and in \202 ammation Systemic in \202 ammation/multi-organ failure \200\224causes Exposure to an exogenous insu lt can result in an exaggerated, generalized, and often inappropriate systemic in \202 amm atory response syndrome ( \200\230SIRS \200\231). Stimulation of in \202 ammatory pathways leads to activation of macrophages, endothelium, neutrophils, platelets, coagulation, \201 brinolytic and contact systems with release of in \202 ammatory mediators and effecto rs (e.g. cyto- kines, prostanoids, proteases, free oxygen radicals, nitric oxide, endotheli n). This results in microvascular abnormalities, blood \202 ow redistribution, endo- thel ial swelling, loss of tight junctions between cells, interstitial oedema and \201 brosis, and mitochondrial dysfunction. The consequences of this may be organ dysfunction, varying from \200\230mild \200\231 to severe, and affecting single or mul- tiple organs. This may result in combinations of cardiovascular collapse, gas- trointestinal failure, renal failur e, hepatic failure, encephalopathy, neuropathy, myopathy, and/or disseminated intravascular coagulation. Acute respiratory distress syndrome (ARDS) and its milder variant acute lung injury (ALI) are the respiratory components of this pathophysiological response. Causes include: \200 \200 \200 \200 \200 \200 Infection. Trauma, burns. Pancreatitis. Inhalation injuries. Massive blood loss/transfusion . Miscellaneous including drug-related (including overdose), myocardial infarction, drownin g, hyperthermia, pulmonary embolus. De \201 nitions Systemic in \202 ammatory response syndrome (SIRS) Two or more of: \200 \200 \200 \200 Temperature >38*C or <36*C. Heart rate >90bpm. Respiratory rate >20 breaths/min or PaCO2 <3 2mmHg (4.3kPa). WBC >12,000cells/mm3, <4000/mm3, or >10% immature forms. Sepsis The systemic response to infection. De \201 nition as for SIRS but as a result of i nfection. Severe sepsis Sepsis associated with organ dysfunction or hypoperfusion. These may include, but are not limited to, lactic acidosis, oliguria, or an acute altera- tion in mental stat us. Septic shock Sepsis with hypotension, despite adequate \202 uid resuscitation, plus pres- ence of perfusion abnormalities. Multi-organ dysfunction syndrome (MODS) Presence of altered organ function in an acutely il l patient such that homeostasis cannot be maintained without intervention. Multiple organ f ailure (MOF) has not achieved worldwide uniformity of de \201 nition. SYSTEMIC INFLAMMATION/MULTI-ORGAN FAILURE \200\224CAUSES 557 See also: Acute respiratory distress syndrome (1), p360; Acute renal failure \200\224diagno sis, p400; Abdominal sepsis, p422; Pancreatitis, p424; Infection \200\224diagnosis, p552; P yrexia \200\224causes, p602. 558 CHAPTER 31 Infection and in \202 ammation Systemic in \202 ammation/multi-organ failure \200\224management Treatment is largely supp ortive though the cause should be removed/ treated, if at all possible. Treatment includes antibiotics, drainage of pus, \201 xation of femoral/pelvic fractures, and debridement of necrotic tissue. An important facet of organ support is to minimize iatrogenic trauma. It is suf \201 cient to maintain survival with relative homeostasis until recovery takes plac e rather than attempting to achieve normal physiological or bio- chemical target values. An example of this is permissive hypercapnia.