Ernest L. Mazzaferri, Jr., MD, FACC

• Associate Medical Director
• Richard M. Ross Heart Hospital
• Assistant Professor, Interventional Cardiology
• The Ohio State University

Close liaison with haematologists in the peri-operative period is key to ensure that levels of clotting factors are optimal medicine 665 buy nitroglycerin 6.5 mg with mastercard. Sickle cell disease ­ sickle cell patients often require orthopaedic surgery and careful liaison with the haematologists is needed and may involve exchange transfusion (for severe homozygous disease) medications xerostomia order 2.5 mg nitroglycerin fast delivery. Ankylosing spondylitis ­ these patients present difficulties with airway management silent treatment order 6.5 mg nitroglycerin with visa, restrictive respiratory disease and cardiac defects (pump and valves) symptoms carpal tunnel cheap 6.5 mg nitroglycerin amex. They may require post-operative intensive care symptoms of high blood pressure 2.5 mg nitroglycerin order with mastercard, and should be discussed with the anaesthetist. Post-transplant surgery, particularly renal and liver transplants ­ these patients are often on immunosuppressive agents. It is important to avoid modifying any of their medication without discussion with the transplant physicians. In addition, certain medications may need to be avoided or the doses altered in the presence of renal and liver transplants. It is advisable to ask the transplant physicians looking after these patients if they should be transferred to that centre for surgery (there may not be time if the surgery is emergent). The answer will often (but not always) be yes, especially for patients with liver and multivisceral transplants. One of the pillars of orthopaedic surgery is to aim for mobilisation and rehabilitation as rapidly as the surgery will allow (Table 19. Most orthopaedic surgery allows for immediate mobilisation, but this aim may not be realised because of post-operative pain. One of the key aspects of successful orthopaedic peri-operative care is the control of pain. There are many aspects involved in controlling pain and they can be categorised as pre-operative, peri-operative and post-operative. There are some analgesic medications to be avoided in certain orthopaedic patients. These fractures rely on the inflammatory response to heal which may be diminished by the prolonged use of anti-inflammatories. Often performed in pre-op classes Some evidence it may reduce postoperative pain Can be used to help position patients with fractures before performing regional techniques. Care with hallucinations Drowsiness, gastrointestinal symptoms Recent evidence to show reduced opiate consumption post-operatively Potential hypotension. In many orthopaedic operations a significant amount of equipment is needed, including simultaneous fluoroscopy. The need for X-rays during the procedure must be taken into account when selecting an operating table and positioning the patient. Often complex positions are used with patients elevated up high or turned prone where airway, venous and other access may be more complex. Care must be taken to ensure these risks are controlled prior to prepping and draping the patient, when it becomes much more difficult. Chapter 19: Orthopaedic cases 229 Intra-operative management Blood loss Pre-operative haemoglobin can be optimised and blood can be grouped and saved or crossmatched to allow rapid access if blood products are needed. Tranexamic acid is also used routinely to minimise blood loss in lower limb joint replacement surgery (its use is contra-indicated in patients with a personal history of thromboembolic disease and some centres avoid using it in patients with coronary stents). Infection control Whenever surgical implants are used, it has been shown that prophylactic antibiotics can reduce the risk of infection. The antibiotic should have reached peak tissue concentration at the time of the incision. The exact pharmacological agent used is often determined by local policy, but it will be effective against gram-positive organisms such as Staphylococcus aureus. It is generally accepted that many cephalosporins are contraindicated in patients over the age of sixty because of the risk of developing Clostridium difficile infections. Post-operative infection is more common where there is a focal area of sepsis elsewhere on the patient, particularly distal to the proposed surgical area For this reason, where possible, surgery should be delayed until concomitant infections are fully resolved. There is no consensus on the duration of prophylactic antibiotics, but typical local protocols suggest a single pre-operative dose or one pre-operative and three post-operative doses (or 24 hours, whichever is the sooner). Common hip surgery cases the hip is one of the most common anatomic sites for surgery, particularly in children, the retired and the elderly. In retired patients the surgery is most often elective hip replacement surgery and in the elderly urgent hip fracture surgery. Evidence has shown that proceeding to surgery within the first 36 hours from admission is associated with a better outcome and for this reason tests that may delay surgery, such as echocardiogram for a heart murmur, are not performed unless they can be done rapidly. The general principle with hip fractures is that they need to be fixed as soon as possible and tests that will not make immediate surgery safer should be delayed until the post-operative period. Often senior anaesthetic input is needed to make these delicate decisions on a patient by patient basis ­ for example, when echocardiography is not rapidly available, by assuming that a patient with an uncharacterised systolic murmur may indeed have aortic stenosis, and providing care (intra-operative and post-operative) based on that assumption: invasive monitoring, peri-operative inotropes and high-dependency post-operative care. This remains a topic of national interest with current multicentre studies set up to try and provide therapeutic suggestions. Hip fracture patients anticoagulated with warfarin should be given vitamin K unless contra-indicated. Fresh frozen plasma should not be routinely administered, but only considered when vitamin K is contraindicated. It should be given six hours after surgery and continue for 28 days unless contra-indicated. Mechanical prophylaxis with graduated compression stockings and foot or calf pumps should also be considered. Both hip fracture patients and elective hip replacement patients should receive prophylactic antibiotics. There is also an indication for the use of tranexamic acid, particularly in hip arthoplasty. In hip arthroplasty, bone cement is often pressurised inside the intramedullary canal to secure the prosthesis. There is the risk that emboli or possibly a reaction to the cement may cause a systemic effect that can, in rare circumstances, be fatal. Adequate cleaning and preparation of the canal may help to avoid this and in very fragile patients overpressurisation of the cement should be avoided. In certain types of hip fracture a long Chapter 19: Orthopaedic cases 231 intramedullary femoral nail may be needed and this may involve reaming the intramedullary canal. This can lead to the complication of fat emboli and the respiratory compromise that follows. Instrumenting and, in particular, reaming of the intramedullary canal should be avoided in elderly frail patients unless no alternative is available. Where hip fractures are pathological, secondary to multiple femoral metastases, consideration should be given to venting the femur distal when instrumenting the canal to avoid systemic emboli. Elective hip surgery offers the advantage of allowing a comprehensive pre-operative assessment. Particular attention is paid to the state of the skin on the affected limb, looking for signs of infection or active psoriatic plaques. Liaison with any relevant specialties can also be carried out depending on the co-morbidities. As mentioned above, a key element of the pre-operative assessment is the mental preparation of the patient for surgery. Enhanced recovery programmes for joint replacement have seen a high level of patient satisfaction and have resulted in significantly reducing the average length of stay after hip replacement. The specific type of anaesthetic chosen for hip replacement should aim to minimise post-operative nausea and pain, but leave motor function intact to allow day of operation mobilisation whenever possible. Elastomeric pumps with continuous intra-articular infusion of low-dose local anaesthetic may contribute to effective multimodal post-operative pain relief after hip replacement and have the possible advantage of reducing morphine consumption. Common knee, foot and ankle surgery cases One unique factor of operating on the knee, foot and ankle areas is the common use of a tourniquet. The use of pneumatic tourniquets is recommended because the pressure can be directly controlled. If the tourniquet is left up for more than two hours an appreciable rate of permanent neurological damage occurs. The pressure of the tourniquet should not exceed more than 150 mmHg greater than that of the systolic blood pressure. It is important that the surgeon and anaesthetist communicate clearly when the tourniquet is to be let down. After major operations, such as knee replacement, unless contra-indicated, tranexamic acid should be administered as the tourniquet is let down. When operating around the knee, tibia, ankle and foot there is a higher possibility of developing compartment syndrome of the leg during some types of surgery (particularly fracture fixation). For this reason, a pre-operative discussion between the anaesthetist and surgeon needs to take place to identify the risk of compartment syndrome and to determine whether or not a regional block is advisable. A regional block may mask the symptoms of an evolving compartment syndrome and when the risk is high, many centres avoid the use of such blocks. The severe pain of compartment syndrome may breakthrough peripheral nerve blockade and, if clinically suspected, direct compartment pressure monitoring or alternative tests Where patients are expecting to go home a few hours after their operation, there is an imperative for immediate post-operative mobilisation. A common choice is a general anaesthetic and local infiltration of anaesthetic around the wounds in the knee (field block). For most knee, foot and ankle operations a combination of local anaesthetic infiltration in the wound or localised blocks Total knee replacement is an example of a very common orthopaedic operation where patients are normally kept in for two or three days after the operation. They should undergo a thorough pre-operative assessment, as for total hip replacements. However, even more emphasis is placed on the pre-operative exercise regime and the prehabilitation in order to achieve early range of movement. Day of surgery mobilisation has been shown to be key to enabling enhanced recovery. Minimising loss of motor function around the knee and post-operative nausea, while keeping pain fully under control, are the aims of a successful anaesthetic in knee replacement surgery. Common choices include general anaesthetic or spinal anaesthetic with a high-volume, low-concentration, local anaesthetic infiltration field block. If peripheral nerve blocks are used they are focused on the sensory supply of the knee or designed to have short enough duration, to allow early mobilisation. Physiotherapy on the day of surgery is very important, both for hip and especially knee replacement surgery. It is very effective at pain relief, but does have the side effects of post-operative nausea and does make mobilising more complicated. A continuous intra-articular infusion of high-volume, low-concentration local anaesthetic However, some surgeons Chapter 19: Orthopaedic cases 233 have concerns about the risk of infection. This can be alleviated somewhat by using closed elastomeric pumps that can be loaded by the surgeon in the sterile field, sealed and left for two to five days and then removed on the ward. Other cited disadvantages include the possibility of reduced mobilisation because of being encumbered by lines. This is less so again with elastomeric pumps because they do not require a power supply and are small. It is likely that we will see increasing use of elastomeric intra-articular infusion pumps after both hip and knee replacement surgery in the future. Common upper limb cases Pre-operative tests for surgery on the upper limb are similar to that for the lower limb. A typical combination would be a regional block with or without a general anaesthetic. For the shoulder, an interscalene brachial plexus block is often used and for the elbow, forearm and hand, the supraclavicular brachial plexus block. The axillary plexus block is less predictable but may be useful in certain circumstances (less risk of pneumothorax and almost no diaphragmatic paresis). For shoulder surgery in patients with respiratory disease some anaesthetists may use a combination of suprascapular and axillary nerve blocks to avoid the risk of diaphragmatic paresis. Because the blocks can be long lasting, liaison between surgeon and anaesthetist regarding the risk of compartment syndrome is important. In addition, patients discharged home with an active block must be warned to be very careful with the affected limb which is at risk of injury The best strategies to avoid this are using a sling where appropriate and teaching the patient to control the blocked arm by using the nonblocked limb to hold it. Continuous infusion pumps, particularly elastomeric pumps, have an important role in post-operative pain relief in shoulder and elbow surgery. The continuous infusion is similar to that for hip and knee replacements, but it is not typically intra-articular, but rather into the area where the block is placed around the plexus or in the subacromial space. Patient positioning is important in all surgery, but particularly so in surgery of the shoulder and elbow. The operating field is very near to the airway and care must be taken to avoid disturbing the airway during the operation. Patients can normally tolerate a tourniquet, without an anaesthetic for a limited period Many patients will find it difficult to tolerate lying still in one position for more than about an hour without experiencing aches or pain in their neck, back, knees and shoulders. The operative area remains numb but they end up having systemic opioids for their positional discomfort, increased sedation or even general anaesthesia in order to cope. Adrenaline is never mixed with local anaesthetic for a ring block as it may cause irreversible digital ischaemia. The shoulder, elbow and hand joints are particularly prone to post-operative stiffness. This can be minimised by pre-operative patient education classes similar to those used in knee and hip replacement, to explain to patients the post-operative rehabilitation exercises and to start prehabilitation. Other post-operative considerations Some surgery on the limbs can result in significant fluid shifts. In the immediate post-operative period, care must be taken to maintain an accurate fluid balance and maintain vital organ function through adequate tissue perfusion and oxygenation. Where major surgery is contemplated, or any surgery on particularly fragile patients, it is recommended that high-dependency care be used in the post-operative period to allow close monitoring.

During this period there is also bacterial overgrowth which then invades the disrupted mucosal barrier layer symptoms of depression purchase 2.5 mg nitroglycerin with amex. To this end medications and grapefruit nitroglycerin 6.5 mg order with amex, research regarding intestinal maturity in the preterm neonate medications used to treat adhd buy nitroglycerin us, altered intestinal microbial colonization medicine 7 day box purchase 6.5 mg nitroglycerin with visa, and immature circulatory regulation of the premature intestine is being actively pursued medications ranitidine discount 6.5 mg nitroglycerin overnight delivery. Suspected disease Systemic signs Temperature instability, lethargy, apnea, bradycardia Poor feeding, emesis, abdominal distension, fecal occult blood Distension with mild ileus Significant bowel distension, small bowel thickening, pneumatosis intestinalis, persistent bowel loops, portal venous gas. Neonatal necrotizing enterocolitis: therapeutic decisions based on clinical staging. The reasons for this are unclear and further research, looking at whether this is a causative phenomenon versus an indicator of severe illness, needs to be pursued. Amongst these, the most common is sepsis, which frequently manifests in the neonate as distention, emesis, and temperature instability, as well as altered white blood cell count. A generalized ileus from other conditions may also present as abdominal distention and emesis such as severe enterocolitis associated with Hirschsprung disease. It can be seen as a relative lucency overlying the liver on a plain supine abdominal radiograph (28. On a left lateral decubitus film, the pneumoperitoneum can be seen as air subjacent to the liver (28. The area over the liver appears more radiolucent in this radiograph, concerning for perforation (arrow); 28. Serial physical examination, radiography, and laboratory evaluation are used for surveillance. Few data exist regarding optimal antibiotic regimens and duration of therapy, although broad-spectrum coverage based on resistance patterns within an individual neonatal intensive care unit is recommended. Additionally, in severely ill patients who remain refractory to broad-spectrum coverage, addition of antifungal agents should be considered. Also, patients who develop profound thrombocytopenia and are coagulopathic consistent with disseminated intravascular coagulation should be treated with platelet and plasma transfusions as appropriate. The most clear-cut indication for an operation is evidence of intestinal perforation ­ most frequently diagnosed as the presence of free intraperitoneal air on a plain abdominal radiograph. A relative indication is rapid and/or progressive clinical decline despite escalation of medical support. This clinical decline can manifest as worsening acidosis, increased abdominal distention, thrombocytopenia, bowel obstruction on an abdominal radiograph, or the development of abdominal wall discoloration or erythema which can be associated with bowel necrosis and perforation. The choice of surgical technique has been the subject of much debate over the past several decades. Often, the clinical stability and gestational age of the patient help guide the decision of whether to perform a traditional laparotomy with bowel resection versus placement of a peritoneal drain. In several studies, patients who had a peritoneal drain placed because they were too unstable to undergo an abdominal exploration had a reported mortality of approximately 50%. The technique of peritoneal drainage involves making a small incision on the lower abdomen (28. More often than not, focal areas of necrosis are identified with intervening normal bowel. Options for the remaining bowel include reanastomosis versus ostomy formation (28. In a small fraction of patients, such as those with pan-intestinal necrosis or in patients with areas of marginal viability, a second-look laparotomy is warranted in order to preserve optimal bowel length. Once bowel function has returned, as evidenced by production of stool, enteral feeds are reinitiated with extreme caution to ensure patients will tolerate this new stress to their intestinal tract. Closure of the ostomy is often delayed for several weeks to months to allow for patient growth and to diminish the risk of further injury to the bowel secondary to immature scar formation. These patients will manifest with feeding intolerance after either reinitiation of feeds or as feeds are increased to a determined goal. Stricture formation can be further evaluated with a contrast enema which will show a transition zone at the area of the stricture. If a stricture is present, surgical resection or stricturoplasty is indicated in order to alleviate the obstruction. Short bowel syndrome occurs after an extensive resection, leaving inadequate bowel length to allow for nutritional absorption. These patients may ultimately require bowel lengthening procedures or small bowel transplantation. A comprehensive nutrition care plan includes individual nutrient requirements, intake goals, and objectives for nutritional care as well as the route of nutrition administration. Careful, ongoing monitoring and evaluation using standardized growth charts allows for prompt intervention when any deviation from the expected growth rates is detected. Gastric feeds are more physiologic than direct intestinal feeds and allow a more normal digestive process and hormonal response to feeds. Bolus feeds and a higher rate of feeding volume infusion are possible with the stomach acting as a reservoir. Contraindications to gastric feeds may include gastroparesis, severe gastroesophageal reflux, persistent or severe emesis, aspiration risk, dumping syndrome, or pancreatitis. The smallest diameter tube should be placed in this setting while considering the size of the patient as well as the rate and viscosity of enteral product to be infused. For the critically ill child, there are insufficient data to recommend gastric versus transpyloric feedings. Transpyloric feeding may improve caloric intake when compared to gastric feeds in such a clinical setting. Postpyloric feeding may be considered in children who have failed a trial of gastric feeding or who are at high risk of aspiration. Gastric feeds can be given as a bolus, continuous drip, or as a combination of the two methods. Testing (endoscopy, pH/impedance monitor) may be needed to determine if a fundoplication or other antireflux procedure is required before placement of a gastric feeding device. Jejunal (intestinal) feeds bypass the stomach which can be helpful in clinical scenarios such as gastroparesis, but they also bypass gastric acid digestive and bactericidal processes (29. Nutrition Overview 255 no gastric reservoir available, jejunal feeds require continuous drip infusions over a long duration. Hyperosmolar formula products might not be well tolerated using this route as they may lead to dumping syndrome. In the critical care setting, pediatric patients receiving jejunal feeds may be able to advance to caloric feeding goals more quickly compared to adults. Because jejunal tubes are usually long and small in diameter, they have an increased incidence of clogging; administration of certain medications and inadequate or improper flushing are a major cause for clogging. Considerations in deciding the feeding schedule include the location of the enteral access device (gastric or jejunal), the clinical condition of the patient, and feeding tolerance history. Continuous feeding may be considered for the critically ill child with hemodynamic instability, abdominal distension or discomfort, or vomiting with bolus feedings. Patients with malabsorption or short bowel syndrome may experience improved absorption with continuous infusion of feeds. Nocturnal continuous feeds may be used as an adjunct to an oral diet in patients who are unable to ingest adequate calories and nutrients during daytime hours. Continuous feeds require an infusion pump for a consistent rate of formula delivery. Combination feeds of both bolus and continuous feeds are also a consideration depending on the clinical scenario. However, it is important to involve a registered dietician in the management of patients with complex nutrition issues to prevent worsening malnutrition, obesity, or the complications of refeeding syndrome (such as hypophosphatemia and other electrolyte abnormalities). Anthropometrics, including weight, height, and body mass index, are essential in determining initial and follow-up dietary goals of patients. Specific laboratory data will be needed in nutrition management, including serum electrolytes, magnesium, calcium, phosphorus, and triglyceride levels. Other laboratory parameters, such as zinc, iron, or vitamin B12 levels, will be necessary to monitor depending on the clinical scenario. Two buds, a dorsal and a ventral, develop from the endodermal lining of the primitive duodenum. The ventral pancreatic bud migrates dorsally, forming what will become the inferior head and uncinate process of the pancreas. In most cases, the main pancreatic duct (of Wirsung) is formed by fusion of the entire length of ventral duct as well as a portion of the distal dorsal duct. The proximal portion of the dorsal duct forms the accessory duct (of Santorini), which enters the duodenum by way of the minor papilla. Most pediatric pancreatic abnormalities result from alterations of this development (30. It is caused by a failure of the ventral ductal system to fuse with the distal dorsal ductal system. Options include endoscopic dilation, papillotomy, and sphincterotomy of the minor papilla, with or without stent placement (30. Most (70%) are associated with congenital bile duct dilation and choledochal cysts or biliary cysts. There is regurgitation of pancreatic juice into the biliary tree (pancreatobiliary reflux) and of bile into the pancreatic duct (biliopancreatic reflux). Because of an increased risk of cholangiocarcinoma, surgical resection with cyst excision and cholecystectomy is recommended. The next major classification of congenital anomalies are the disorders of migration. These defects result during the progression of embryologic development, as the progenitor tissue makes its way to its final destination. Ectopic pancreas, or a pancreatic rest, is pancreatic tissue that lacks anatomic or vascular continuity with the pancreas. The majority of ectopic pancreatic tissue is found in the foregut, with 75% in the stomach, particulary the prepyloric gastric antrum (30. Other reported locations are at the gallbladder, bile ducts, the minor and major papillae, and within a Meckel diverticulum. Typically, these lesions are discovered incidentally during endoscopy, surgery, radiographic contrast studies, or at autopsy. They most commonly consist of exocrine cells, although endocrine pancreatic tissue and a combination of exocrine and endocrine cells have also been reported. When symptomatic, rests may require resection by endoscopic snare or band ligation, but surgical resection is indicated if the muscularis propria is involved. Annular pancreas is a rare congenital anomaly in which a segment of the head of the pancreas either partially or completely encircles the second part of the duodenum. Annular pancreas has a prevalence of about 1 in 2,000 persons and can occur either as an isolated finding or with other congenital abnormalities such as Down syndrome, esophageal and duodenal atresia, imperforate anus, and Meckel diverticulum. The third hypothesis is that there is abnormal hypertrophy of both ventral and dorsal buds that fuse before rotation and thereby encircle the duodenum. Whereas one-half to twothirds of adult cases of annular pancreas remain asymptomatic and are found incidentally, the majority of children with annular pancreas develop gastric outlet obstruction within the first few days of life. The most common pediatric presentation is a neonatal small bowel obstruction just proximal to the ampulla of Vater. Newborns can present with feeding intolerance, bilious vomiting, and abdominal distention. Children with annular pancreas have a higher association with other congenital abnormalities, the most common being Down syndrome and congenital heart disease. In this very young age group, surgical correction is immediately indicated, and confirmation of annular pancreas is made during laparotomy. Treatment aims to bypass the obstruction without transecting the pancreatic tissue. Resection of the annulus is usually avoided because of the risk of pancreatitis, pancreatic fistula formation, or an incomplete relief of the obstruction. The prognosis of patients with annular pancreas depends on the age of onset of symptoms. Infants present with neonatal insulin-dependent diabetes mellitus, intrauterine growth retardation, subsequent failure to thrive from pancreatic insufficiency, and they require pancreatic enzyme replacement therapy. These syndromes show fatty or fibrous replacement of the pancreas and are described in more detail in Chapter 31, Exocrine Pancreatic Insufficiency. In severe cases, the fat malabsorption can lead to deficiencies of fat-soluble vitamins A, D, E, and K. Routine vitamin supplementation has made clinically evident vitamin deficiency now uncommon. Therefore it is important to maintain adequate levels of vitamin in D in these patients. Insufficient secretion of pancreatic enzymes (proteases, amylase, lipase, colipase) An adequate sweat specimen can be collected for sweat chloride (Cl-) in infants starting at 2 weeks of age, ideally weighing at least 2 kg. Shortening the sampling times and failing to correct for intestinal losses have led to misclassification of pancreatic sufficient patients as insufficient. Indirect tests are widely available and easier to perform but have low sensitivity and specificity. In children younger than 6 months of age, a fecal fat greater than 15% of fat intake is considered abnormal although this value is 7% for children over 6 months of age. Fecal fat excretion does not discriminate among hepatobiliary, intestinal mucosal, or pancreatic causes of fat malabsorption. Fecal elastase-1 the measurement of fecal trypsin and chymotrypsin tests may be inaccurate due to intraluminal degradation and cross-reactivity with ingested enzymes. In healthy individuals, only small amounts of trypsinogen should be present in serum. The direct tests involve the collection of pancreatic fluid secreted into the intestine and measurement of enzymes (pancreatic acinar function), and fluid volume and electrolytes (pancreatic ductal function).

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Retraction on a swollen brain results in underlying ischaemia or even contusion with detrimental post-operative swelling medicine 5513 buy discount nitroglycerin 2.5 mg on-line. In the presence of hydrocephalus and ventriculomegaly medicine bow national forest purchase nitroglycerin online pills, a ventriculostomy is effective treatment refractory 2.5 mg nitroglycerin order otc. Prolonged hyperventilation should not be used as it may increase the volume of ischaemic brain medicine 3 times a day buy nitroglycerin no prescription. Commonly used options include a dose of mannitol 20% (which is also a free-radical scavenger) medicine of the wolf order nitroglycerin 6.5 mg free shipping, elevating the blood pressure (to promote collateral circulation), mild hypothermia and propofol in doses achieving burst suppression. In some complex and large aneurysms it is desirable to lower the tension within the sac at the time of clip application and brief cautious induced hypotension may be an alternative to temporary clipping of the parent artery. For more complex lesions particularly with awkward access to place a more proximal temporary clip, intravenous adenosine administration resulting in brief cardiac asystole allows the optimum clip application. Posterior fossa surgery Positioning precautions are applied in the prone or the lateral/park-bench positions. For motor recordings short-acting muscle relaxants are used for endotracheal intubation, and no further doses are given. Profound vagal mediated bradycardia may necessitate anticholinergic administration to block the reflex activity. Pre-existing or post-surgical lower cranial nerve deficits may result in multiple complications mainly because of aspiration from bulbar palsy and rarely stridor from bilateral involvement. Whenever these are present or anticipated a nasogastric tube is placed peri-operatively for feeding and if respiratory complications from aspiration occur or extensive bulbar dysfunction is likely to be prolonged then a temporary tracheostomy is considered. Cardiovascular and respiratory centre dysfunction following surgical manipulations of the floor of the fourth ventricle would necessitate post-operative ventilation. Vomiting is frequently seen following posterior fossa surgery and care for airway protection should be observed during extubation and in recovery until full consciousness is regained. The use of regular post-operative anti-emetics is considered at an early stage in addition to those given intra-operatively. In urgent cases, such as for pituitary apoplexy, hydrocortisone administration covers the potential hypocorticism resulting from pituitary hypofunction and the diminished pituitary reserves to deal with the additional surgical stress. In patients with acromegaly, growth hormone excess may cause hypertension, diabetes, cardiomyopathy and sleep apnoea. In cases presenting with significant sleep apnoea, post-operative planning for airway management is important, particularly if nasal packs are placed following trans-sphenoidal surgery. This group in addition is more vulnerable to develop systemic infections and deep vein thrombosis. Post-operative monitoring and correction of electrolyte disturbances, particularly the serum sodium levels, is particularly important and awareness of the fact that fluctuations frequently occur (see Table 17. Adequate local anaesthetic infiltration of the scalp with knowledge of the regional cutaneous sensory nerve supply is one of the key elements for successful anaesthesia. Commonly the patient is anaesthetised for the first part of the procedure to allow the craniotomy to be performed, and occasionally some tumour resection. The recognition of hypoventilation during these periods should be as early as possible and counteracted otherwise detrimental effects including uncontrollable brain swelling may be difficult to control. The use of cortical stimulation to map the eloquent cortical, and more recently the subcortical brain regions, requires fully co-operative patients with no residual effects of muscle relaxants or sedation. Seizures are commonly associated with the intrinsic lesions that require awake craniotomy and may be induced by motor cortical stimulation intra-operatively. Therefore adequate prophylactic anticonvulsants should be administered and the therapeutic dose should be reached in those presenting with epilepsy prior to the procedure. Seizures can often be rapidly terminated intra-operatively by applying ice-cold saline to the stimulated area. This allows the procedure to continue without the need to resort to general anaesthesia. Spinal surgery Anterior cervical approaches involve partial retraction of the pharynx to gain access to the spine. Fibre-optic intubation to avoid manipulation of the unstable cervical spine is considered in those cases requiring surgery following trauma, degenerative disease with subluxation and some spinal tumours. In the prone position, care should be taken to ensure adequate chest support and an abdomen with free movement. Both prevent compression of the major intra-abdominal vessels, which could lead to epidural venous engorgement as blood diverts away from the compressed intra-abdominal vessels to return to the heart. This also allows minimal inflation pressures to ventilate the lungs, thus minimising intrathoracic pressure. Neuroprotection to the spinal cord is analogous to cerebral neuroprotection particularly after spinal cord injury, surgery for vascular anomalies or intrinsic cord lesions. Monitoring both motor and sensory function is becoming standard for surgery involving intrinsic spinal cord lesions and during corrective surgery for spinal deformities. Blood loss can be excessive in spinal surgery and hypotension resulting in cord hypoperfusion can cause cord infarction, especially in cases of spinal cord lesions or swelling and in the elderly. Blood pools in dependent body parts Decreased ­ unopposed vagal tone, worsened by hypoxia and endobronchial suction Disrupted autonomic pathways Neurology Loss of sensation and motor power below the level of injury, with gradual return of reflexes. Initially flaccid paralysis, but over time spasticity and hyperreflexia develop Spinal cord injury Initially maintain spinal cord perfusion. Later supportive measures and rehabilitation Cause Treatment Severe brain injury, cervical or high thoracic spinal cord injury Exclude haemorrhage. Vasopressors and vagolytics (atropine) may be necessary Multi-modal analgesia intra-operatively and in the post-operative period ensures mobilisation following major procedures. Exaggerated or obtunded spinal reflexes following cord injury may result in positional hypotension, which is particularly sensitive to hypovolaemia and may be associated with bradycardia. Autonomic dysreflexia is a pathological reflex that can cause profound hypertension leading to stroke and death if left untreated. Patients with a spinal cord injury above T5 are most susceptible, although it can occur in patients with lesions between T6 to T10. Cases that precipitate the hypertensive crisis are those performed below the umbilicus ­ most commonly urological procedures. A surge in blood pressure in patients having spinal surgery and an existing spinal injury should arouse suspicion of a blocked/kinked urinary catheter or urinary retention. Transthoracic approaches to the spine require endobronchial intubation to allow deflation of a lung and access to the thoracic spine. In extreme cases induced hypotension is needed to continue in the post-operative period for 24­48 hours. Adequate spontaneous ventilation and conscious level to protect the airway should be insured prior to extubation. Airway protection may be compromised by diminished conscious level, in patients with bulbar dysfunction or following procedures resulting in local swelling. This will often require transfer to a highdependency unit for close observation, and intervention if neurological deterioration should occur. When there is a serious risk to the airway, or when neurological recovery is poor, the patient should be transferred ventilated to the intensive care unit. Some neurointensive care units have the benefit of multi-modal brain monitoring, permitting earlier detection and treatment of problems in the sedated, ventilated patient. The acuity and uncertainty of the extent of the injuries require the anaesthetist to be both vigilant and methodical as the case progresses. The anaesthetist should take an active lead in the operating theatre, in combination with the senior surgeon present, as he/she has the greatest situational awareness and needs to be aware of the resources at his/her disposal. There are three central tenets to the damage-control philosophy: permissive hypotension, damage-control or haemostatic resuscitation, and damage-control surgery. The damage-control philosophy was initially conceived as a surgical approach to the multiply injured patient when it was realised that such patients lacked the physiological reserve to survive complex reconstructive surgery and restoration of anatomy. Damagecontrol surgery is confined to that surgery which is necessary to control haemorrhage and limit contamination. Temporary cavity closure further abbreviates the surgery and the patient is then normalised physiologically in the intensive care unit before definitive anatomical repair 24 to 72 hours later. However, such an approach to a severely traumatised patient cannot be used in isolation. Haemorrhage leads to hypoperfusion and decreased oxygen delivery, a switch to anaerobic metabolism, lactate production and metabolic acidosis. Heat production is limited in an anaerobic metabolic state and this is exacerbated by exposure and the administration of cold fluid and blood. A temperature of less than 35° C is an independent predictor of mortality in trauma. Trauma patients have an established early coagulopathy related to hypoperfusion and initiated by tissue injury. Furthermore, hyperfibrinolysis also appears to contribute to the coagulopathy of trauma. It has also been shown that patients with a coagulopathy on arrival in the emergency department have a four-fold increase in mortality. Haemostatic resuscitation is an attempt to address the problem of the coagulopathy seen in massively injured patients from whatever cause. Permissive hypotensive resuscitation, in the pre-hospital environment in particular, results from the recognition that aggressive fluid resuscitation may exacerbate blood loss by interfering with haemostatic mechanisms and dislodging clot, especially where haemorrhage is into the torso, which is not controllable with direct pressure or tourniquets. Resuscitation fluid administration is restricted until surgery when the source of the haemorrhage can be controlled. The main drawback of this approach is the acceptance of a period of sub-optimal end-organ perfusion until definitive control of the haemorrhage is achieved. The damage-control philosophy is designed to incorporate its three central tenets concurrently. Damage-control resuscitation, incorporating balanced or hypotensive resuscitation, occurs throughout the pre-hospital, the emergency department, the operating theatre damage-control surgery phase and beyond into the intensive care management. In order to facilitate this, communication and co-operation between the anaesthetists and surgeons is vital. Regular updates between the two parties should occur at specific times and every ten minutes during the operative phase of management. The patient should be receiving maximal oxygen flow via a tight-fitting mask with a non-rebreathing reservoir bag, which should deliver a fractional inspired oxygen concentration (FiO2) of 0. This conveys the duration of paralysis and the muscle relaxant used so that the anaesthetists will have an estimate of the time for the next dose of muscle relaxant. Therefore all patients must be considered to be at risk of aspiration and for cervical spine injury, head injury, hypovolaemia, intoxication, and potentially a difficult airway. Note that an E is added to the numerical value if the patient requires an emergency operation. Intra-osseous needles have revolutionised access because of their speed and success rate. Both need to be established early after the arrival of the patient in the resuscitation department. The anaesthetist is situated at the head and the primary concern is maintenance of the airway and cervical spine control, followed by oxygenation and ventilation. Beware bony fractures to the face, which may compromise the airway despite a jaw thrust. Surgical emphysema from a disrupted airway will cause significant swelling and distortion of the anatomy and an expanding neck haematoma will also obstruct the airway. Stridor, the use of the accessory musculature and paradoxical respiratory movement suggest impending airway collapse. In these situations declining pulse oximetry values, cyanosis, pallor and apnoea are late signs and mandate immediate airway intervention. This is the best way to deliver oxygen in sufficiently high concentrations and effective ventilation. A cuffed tube also ensures protection of the lungs from aspiration and facilitates suctioning of aspirated blood and airway secretions. The indications for a definitive airway are where there is need for airway protection, a reduced conscious level, a need for oxygenation, a need for ventilation and a need to optimise resuscitation (see Table 18. A definitive airway is best placed using direct laryngoscopy and orotracheal intubation. Blind nasal intubation is contraindicated in basal skull fractures, in the presence of expanding cervical haematomas and partial airway obstruction, because of the risk of converting a partial airway obstruction into a complete obstruction. The urgency for airway intubation often dictates the plan but it should always be preceded by a period of optimal pre-oxygenation, and assisted ventilation may be necessary as patients are often hypoxaemic and hypercapneic. An induction agent is administered (typically ketamine, thiopentone or etomidate) and a neuromuscular blocking drug (typically suxamethonium or rocuronium) to facilitate intubation. All induction agents have the potential to produce or exacerbate hypotension and must be used with care, especially in hypovolaemic patients, and at much reduced doses. In general some fluid resuscitation is necessary during induction but should not delay the process. Some re-adjustment of the cricoid pressure and use of a rigid stylet or bougie may be required to improve intubation rates in some difficult-to-intubate patients. It may be pre-loaded with an introducer and have a 10 ml syringe attached to inflate the cuff. Videolaryngoscopy is becoming very common in trauma to try and reduce the time to first intubation and as an aid in difficult intubations. Here, the visual appearance of the oropharynx is divided into four classes depending on the structures visualised. However, the patient needs to be co-operative, upright and to open the mouth fully and protrude the tongue. The difficult airway can be a challenge in trauma as it is seldom possible to stop and return to the issue of a definitive airway later. A difficult airway is defined as one in which a trained, experienced anaesthetist experiences difficulty with mask ventilation, tracheal intubation, or both. It may either be because of intrinsic anatomic airway variability, traumatic injury to the area, or both. Awake intubations may be performed where a difficult airway is anticipated but only in spontaneously breathing, awake, co-operative and haemodynamically stable patients and with the use of a fibre-optic bronchoscope. Where the patient is unco-operative, haemodynamically unstable, or anaesthetised, then spontaneous ventilation should be maintained if possible for intubation.

About 30% of the population of the United States shows evidence of past infection medicine to prevent cold nitroglycerin 6.5 mg buy fast delivery. The infection itself is often asymptomatic medications used for depression buy nitroglycerin 6.5 mg on-line, but can be associated with clinically significant disease and rarely is implicated in acute liver failure treatment 101 cheap nitroglycerin 2.5 mg without a prescription. Sometimes the symptoms are more flu-like with pharyngitis treatment wax cheap nitroglycerin 6.5 mg buy on-line, cough medicines nitroglycerin 2.5 mg amex, runny nose, headache, and myalgias. Physical findings may include jaundice, weakness, pruritis, and tender, slightly enlarged liver and spleen. The incubation period varies from 15 to 180 days and viremia lasts from weeks to years. Most acute infections are self-limited; only 1­5% of adults who become infected progress to chronic hepatitis. Chronic infection is associated with cirrhosis, liver failure, and hepatic cell carcinoma. Histologic changes consist of inflammatory changes with Kupffer cell mobilization and hepatocellular swelling (37. Who should be treated and under what circumstances and for how long is very controversial. Pediatricians are most likely to face this issue when caring for children of recent immigrants from the developing world and children adopted from developing areas. Typically, these children have vertically acquired disease that responds very poorly to interferon treatment. Because of this poor response, in the past it was recommended not to treat vertically acquired disease. However, with the advent of more effective antiviral drugs such as nucleoside reverse transcriptase inhibitors, and the recognition that vertically acquired disease is not as benign as previously thought, the debate about treatment has reopened. A number of geno types and serotypes exist that have important implications regarding treatment and response to treatment. Maternally acquired antibodies can last in the infant up to 18 months, so the antibody-based tests for determining perinatally acquired disease are not reliable before 18 months of age. Since viremia is not always present more than one negative test is needed to declare a patient virus free. Liver pathology will demonstrate generalized necroinflammatory and fibrotic changes, along with lymphoid aggregates in portal areas and sinusoids (37. In adults, the addition of protease inhibitors such as telaprevir or boceprevir (triple therapy), has improved response rates and decreased treatment times; however, no triple therapy regimen is approved for pediatrics and there are no current studies available in children. Yearly evaluation of liver function, viral load, and tumor marker determination (alpha-fetoprotein) as well as yearly abdominal ultrasounds are prudent. Limited information is available regarding the addition of antivirals such as lamivudine. Although rare in the United States, it is extremely common among young adults in developing areas of the world, and recently a number of imported cases have been reported. For the most part it is a short, self-limited disease characterized by jaundice, malaise, anorexia, fever, abdominal pain, and arthralgias. Viral Hepatitis 323 only available on a research basis (through the Centers for Disease Control and Prevention). Nonhepatotropic viruses that may cause hepatitis In immunocompromised individuals and neonates relatively few nonhepatotropic viruses are known to cause hepatitis. Even in simple, self-limited disease, there is almost always a degree of hepatic involvement. Hepatic involvement is encountered in neonates and in immunocompromised individuals. Transmission of the virus can occur transplacentally, during delivery, via saliva, or from breast-milk. An antenatally-acquired infection can be asymptomatic, but it also can be associated with congenital anomalies: low birth weight, microcephaly, cerebral calcifications, chorioretinitis, deafness, and retardation. The liver manifestations include conjugated hyperbilirubinemia and hepatosplenomegaly. Rubella (German measles) Rubella was a common, usually self-limited childhood infection prior to the widespread use of vaccination. It is seen in under-immunized individuals or in immigrants from areas where vaccination is not practiced. If acquired antenatally, rubella is associated with devastating congenital anomalies: ophthalmologic, cardiac, auditory, and neurologic. Transplacental transmission is common if the mother contracts the disease during pregnancy. Rapid diagnosis is important because without treatment, the outcome is universally fatal. However, increasingly there is cross-over and either clinical entity is associated with either viral type. In children under 5 years of age and individuals of any age with immune compromise, parvovirus B19 has been reported to cause a range of liver manifestations from acute hepatitis to fulminant liver failure, and to chronic hepatitis with persistent infection. The virus can be transmitted vertically from mother to fetus, via respiratory tract secretions and via percutaneous exposure to blood. Although patients with parvovirus B19 hepatitis can be quite ill, complete recovery is the usual course, and the need for liver transplantation is rare. Viral Hepatitis 327 Other hepatitis-associated viruses Conclusion There have been huge gains in our knowledge of the process of hepatitis caused by viruses. Progress in prevention has also been made through public health efforts and vaccinations. Treatments are available for many types of viral hepatitis and medical science is on the threshold of introducing more and better treatments. A number of viruses have occasionally been associated with hepatitis especially neonatal liver disease. Thus during its gallbladder phase, bile changes so that sodium concentration almost doubles, bile salt concentration triples, cholesterol increases by fourfold, and bilirubin levels increases about 10-fold. Many of these salts therefore enter a supersaturated state forming the basis for crystallization and stone formation, the usual source of complications and gallbladder pathology. For example, about 20% of children with sickle cell anemia have ultrasound-detectable stones entering adolescence. Other groups at risk for stones include obese children and those receiving oral contraceptives. Stones may cause symptoms by mechanical obstruction somewhere in the biliary tree or at its outlet at the ampulla; or as a predisposition to actual infection and inflammation. Biliary pain is usually felt in the right-upper quadrant, may radiate to the back, is related to fat-laden foodstuffs, and therefore postprandial pain lasts minutes to hours (biliary colic). Transit of stones into the common bile duct may cause obstruction and surgical jaundice, or if blocking the pancreatic duct at the ampulla, acute pancreatitis. Acute cholecystitis may have a bacterial overlay, although chemical-induced inflammation is likely. The right upper quadrant pain and any systemic symptoms are much more pronounced with localized guarding and peritonitis. Sometimes, acute cholecystitis leads to an obstruction at the neck of the gallbladder and failure of drainage with gallbladder distension and pus formation, or an empyema. Pigment stones these are formed from calcium bilirubinate within the gallbladder and are an inevitable consequence of hypersecretion of conjugated bilirubin from the hepatocyte into the biliary canaliculus. This conjugated water-soluble bilirubin is the end-product of the process of red cell degradation and recycling of hemoglobin which begins in the spleen and the reticuloendothelial lymphatic system. In hereditary conditions of red cell deformity, such as sickle cell anemia, spherocytosis, and thalassemia, there is increased red cell turnover and therefore increased throughput of hepatic bilirubin, leading to supersatured bile in the gallbladder and the increased potential for stone formation. As a highly insoluble product, cholesterol is kept in solution by the formation of micelles with bile salts and phospholipid. Again, with increasing solute concentration in the gallbladder this process may be tipped into crystalization and cholesterol stone formation. This sequence is much more multilayered than is the case for pigment stones, and the interplay of underlying factors is complex. Obesity, a family history of gallbladder disease, and the female gender predispose to stone formation in the pediatric age-group as for adults. Bile duct obstruction leads to rising conjugated bilirubin, -glutamyl traspeptidase, and alkaline phosphatase enzyme levels. A raised C-reactive protein and leukocytosis would be expected in any acute inflammatory process. This technique should also be able to measure any degree of biliary tract dilatation suggestive of obstruction, and thickness of the gallbladder wall suggestive of chronicity. Further imaging of the biliary system may be indicated, particularly if there is a history of jaundice or pancreatitis. Magnetic resonance cholangiopancreatography is noninvasive, and in most individuals it is able to delineate the extrahepatic and intrahepatic ducts (38. Radioisotope studies may be able to show whether a gallbladder is functional or not and again detect degrees of obstruction. The underlying cause of stones should be investigated to determine if there is a hemolysis etiology. Cholesterol stones might be suspected if the subject is female, overweight, and with a positive family history of gallbladder disease, although the fasting plasma cholesterol is still usually normal. Cholecystectomy specimen from 15-year-old girl with multiple, idiopathic gallstones. Simple removal of stones during childhood has a high incidence of recurrence and is not recommended. Stones in the common bile duct should be removed, and the easiest method is from below using endoscopic retrograde cholangiopancreatography and sphincterotomy. Alternatively, actual surgical exploration of the duct from above should be rarely needed, but is possible. There is a chance of spontaneous resolution in gallstones dating from infancy where the underlying cause has been removed Cytochrome P450 mono-oxygenases insert an oxygen residue into the compound, rendering the compound more water-soluble but also more toxic. Enzymes attach another residue to the step 1 metabolite, making it even more water-soluble and neutralizing its toxicity. The water-soluble product is extruded into the cannalicular space and secreted with bile. While drugs with this property are rare, acetaminophen (paracetamol) is a well-studied example. Acetaminophen toxicity is treated with N-acetylcysteine, which promotes more glutathione production. Their toxicity is probably related to the great variation in Step 1 and Step 2 enzymes. Among individuals, the enzymes can vary in nucleotide sequence, subtly changing the way they recognize substrates or the speed with which they catalyze their reaction. In both cases, the Step 1 metabolite is thought to bind to hepatocyte proteins, create neoantigens, and in certain individuals stimulate an immune response. It is unclear why this process may occur suddenly even in individuals with a long and previously uneventful history of taking a medication. When Step 1 metabolites damage hepatocytes, children present with a hepatitis picture of nausea, vomiting, anorexia, and elevated transaminases. When Step 1 metabolites injure cholangiocytes, cholestatic symptoms of pruritis and jaundice occur. Step 1 metabolites can also injure any of the other liver cells, including endothelial cells creating a vaso-occlusive disorder picture. The hepatic acinus is the functional unit of the liver and is oriented around the afferent vascular system. The acinus consists of an irregular shaped, roughly ellipsoidal mass of hepatocytes aligned around the hepatic arterioles and portal venules just as they anastomose into sinusoids. The acinus can be divided into zones that correspond to the distance from the arterial blood supply (39. Hepatocytes closest to the arterioles (zone 1) are the best oxygenated, while those farthest from the arterioles have the poorest supply of oxygen (zone 3). This arrangement also means that cells in the center of the acinus (zone 1) are the first to be exposed to bloodborne toxins absorbed into portal blood from the small intestine. Acetaminophen Excessive acetaminophen ingestion is common, accounting for as many as 30,000 reports yearly to the United States National Poison Data System. Ingestion occurs in two forms: 1) an acute overdose, often by adolescents trying to harm themselves; and 2) chronic overdose, by caregivers giving excessive amounts over a series of days. Chronic overdose is particularly difficult to diagnose, because therapeutic doses (75 mg/kg/day) are only slightly less than doses considered toxic (greater than 90 mg/kg/day). Clinically, patients usually present with subtle symptoms including nausea, vomiting, or malaise. Over the course of a few days, liver-specific symptoms ensue, including right upper quadrant pain and elevated transaminases. Liver pathology reveals zone 3 hepatocellular injury, reflecting the higher Hepatotoxins 337 concentration of P450 mono-oxygenases in perivenular hepatocytes. Treatment focuses on delivering N-acetylcysteine as a substrate for glutathione production. It presents with a cholestatic picture when taken chronically, suggesting cholangiocyte or cholangiocyte­hepatocyte damage. Because the hepatocellular injury is found in zone 3, one explanation is that ketoconazole causes contingent hepatoxicity when a Step 1 metabolite abnormally accumulates due to individual variations in Step 2 clearance. However, in severe fungal infections with mild increases in transaminases, some clinicians elect to continue the medication and monitor laboratory values carefully. Clinically, patients can have jaundice as well as abdominal pain, elevated serum transaminases, and hepatosplenomegaly.

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