Dudley Robinson MBBS MD MRCOG

• Consultant Urogynaecologist/Honorary Senior Lecturer,
• Department of Obstetrics and Gynaecology, King? College
• Hospital, London

Biliary drainage may be obtained temporarily by percutaneous transhepatic biliary drainage or directly by endoscopic retrograde biliary stenting blood pressure danger zone ramipril 2.5 mg with visa. Hepatic failure due to massive metastases may produce jaundice arteria transversa colli buy ramipril with visa, pruritus blood pressure up pulse down ramipril 10 mg purchase amex, anorexia arrhythmia mayo clinic purchase genuine ramipril on line, liver capsule pain blood pressure chart english buy ramipril 5 mg mastercard, ascites, disturbances of haemostasis, malabsorption, and electrolyte disturbances, culminating in hepatic encephalopathy. The palliative treatment of liver failure needs to be tailored to the particular symptoms of each patient. Liver capsule pain may be helped by non-steroidal anti-inflammatory drugs or corticosteroids together with conventional analgesics. Symptoms of functional gastric outlet obstruction may be relieved by metoclopramide before meals. Nausea secondary to liver failure may require centrally acting antiemetics such as haloperidol. Naltrexone and stanozolol have also been found to be effective in pruritus from intrahepatic cholestasis and obstructive jaundice respectively (see Chapter 11. Infiltration by tumour Fluid depletion Electrolyte imbalance: · uricacid(tumourlysissyndrome) · hypercalcaemia · paraprotein. Management of gynaecomastia in patients with prostate cancer: a systematic review. Diabetes, cancer, and metformin: connections of metabolism and cell proliferation. Hypoglycemia associated with non-islet-cell tumor and insulin-like growth factors. Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. Bisphosphonate-associated osteonecrosis: a long-term complication of bisphosphonate treatment. The insulin and insulin-like growth factor receptor family in neoplasia: an update. A randomised double-blind study of gallium nitrate compared to etidronate for acute control of cancer related hypercalcemia. Conventional therapies include restriction of dietary protein and sodium, bowel clearance with magnesium sulphate enemas and lactulose, as well as bowel sterilization with the non-absorbed antibiotic rifaximin (Bass et al. Since hepatic encephalopathy is a terminal event in advanced malignancy, these unpleasant treatments are rarely appropriate. The main symptom of encephalopathy is confusion, and after establishing the cause, familiar company, a light and quiet environment, and a regular routine should be provided, together with explanation, reassurance, and reorientation. Portal hypertension and abnormal coagulation predisposes to gastrointestinal haemorrhage. Lactic acidosis In cancer patients, lactic acidosis is most frequently type A, due to impaired tissue oxygenation secondary to hypoperfusion as a consequence of septicaemia shock. Less commonly, type B lactic acidosis occurs with large tumour burdens of haematological cancers. Increased lactate production by tumour cells owing to uncoupled oxidative phosphorylation and glycolysis, and reduced lactate clearance due to liver dysfunction, are implicated in the pathogenesis. Lactic acidosis presents with hyperventilation and hypotension and the diagnosis is established biochemically by the combination of wide anion gap acidosis and raised plasma lactate (> 2 mEq/L). High-volume haemofiltration and intravenous sodium bicarbonate may correct the metabolic acidosis, but should obviously only be used if effective anticancer therapy is available and appropriate (Fall and Szerlip, 2005). Polymerase chain reaction analysis of parathyroid hormone-related protein gene expression in breast cancer patients and occurrence of bone metastases. Increased serum levels of a parathyroid hormone-like protein in malignancy-associated hypercalcaemia. Similarly, radiographic testing may not always confirm the presence of obstruction in the presence of classical symptoms, while at times the radiographic changes may predate the onset of symptoms. Therefore, clinicians caring for cancer patients should always retain a high index of suspicion for this problem. Although it may develop at any time in the disease, it occurs most frequently at the advanced stage, with the highest incidence ranging from 5. Intestinal motility disorders due to a deranged extrinsic neural control of viscera may produce delay in intestinal transit, resulting in a clinical picture similar to bowel obstruction, namely pseudo-obstruction. Concomitant disease, such as diabetes, para-neoplastic syndromes, or previous gastric surgery, may also contribute to dysmotility of this kind. Contributing factors include constipation, due to illness and/or to drugs such as those with anticholinergic side effects including opioids. Pain due to opioid-induced constipation, wrongly treated with increased doses of opioids, may result in faecal impaction producing signs consistent with bowel obstruction (Glare and Lickiss, 1992). Pathogenesis An occlusion of the lumen prevents or delays the propulsion of the intestinal contents from passing distally. The accumulation of non-absorbed secretions produces abdominal distension and colicky peristalsis to surmount the obstacle in the early stage, corresponding to a subobstructive state, possibly still reversible. Although there is little or no through-movement of intestinal contents, the bowel continues to contract with increased uncoordinated peristaltic activity. As a consequence, the bowel becomes distended, stimulating intestinal f luid secretion, thus creating a vicious cycle of distension­secretion, further stretching the bowel wall. This will produce damage in the lumen with a consequent inflammatory response involving the activation of the cyclooxygenase pathway and the release of prostaglandins, potent secretagogues either by a direct effect on enterocytes or the enteric nervous reflex (Mercadante, 1995a). The enlargement of the primary tumour or recurrence of abdominal masses, fibrosis, or adhesions may produce extrinsic occlusion of the lumen. Polypoidal lesions or annular narrowing due to disseminated disease may cause an intraluminal occlusion. This may also explain the finding of a redistribution of blood flow between the obstructed segment and the distal sites. Alterations of splanchnic flow are the basis of the appearance of multiple organ failure syndrome caused or worsened by systemic hypotension commonly observed in the late stage of bowel occlusion (Neville et al. Fluids and electrolytes are sequestered in the gut wall and in its lumen (third space) in the presence of vasodilatation. Metabolic and septic consequences the hypovolaemic state may induce functional renal failure due to a decrease in renal flow and, as a consequence, reduced glomerular filtration. Metabolic disorders in intestinal obstruction depend on the site and duration of the obstruction and are caused by dehydration, electrolyte losses, and disorders of acid­base balance (Chan and Woodruff, 1992). Metabolic alkalosis, hypochloraemia, hyponatraemia, and hypokalaemia will be features of a high-level obstruction, in part due to intestinal stasis of biliary, pancreatic, intestinal, as well as gastric secretions (Mercadante, 1997). There will be acidosis due to ischaemic lesions or septic complications (Scott Jones and Schirmer, 1989). The increased abdominal distension reduces the venous return and may impair pulmonary ventilation as a result of elevation of the diaphragm. It consists of the passage of toxins from the intestinal contents through the intestinal wall into the lymphatic and systemic circulation, or bacterial translocation. This phenomenon results from the increase in endoluminal pressure, stasis, and intestinal ischaemia, together with intestinal gangrene and perforation, commonly observed in the late stages of persisting bowel obstruction. The time course of these events is variable, occurring over several days in malignant mechanical bowel obstruction. Clinical and radiological diagnosis In cancer patients, compression of the bowel lumen develops slowly and often remains partial. The progression may be slow or fast, from partial obstruction to complete occlusion, each producing a different spectrum of symptoms, differing intensity of suffering, and ultimate outcome. Accumulation and increased production of secretions produce the principal symptoms, namely abdominal pain and distension, 14. In large bowel obstruction the pain is less intense, deeper, occurring at longer intervals and spreads toward the colon wall It is due to abdominal distension, tumour mass and/or hepatomegaly it is due to severe dehydration, metabolic alterations but above all it is due to the use of drugs with anticholinergic properties and poor mouth care In case of complete obstruction there is no evacuation of faeces and no flatus It is the result of bacterial liquefaction of the faecal material Biliary vomiting is almost odourless and indicates an obstruction in the upper part of the abdomen. The presence of bad smelling and faecaloid vomiting can be the first sign of a ileal or colic obstruction An overall acute pain which begins intensely and becomes stronger, or a pain which is specifically localized, may be a symptom of a perforation or an ileal or colic strangulation. A pain which increases with palpation may be due to peritoneal irritation or the beginning of a perforation Nausea Colicky pain Intermittent or continuous Variable intensity and localization due to distension proximal to the obstruction; secondary to gas and fluid accumulation most of which are produced by the gut Variable intensity and localization Continuous pain Dry mouth Constipation Overflow diarrhoea Intermittent or complete In case of partial obstruction the symptom is intermittent Reproduced courtesy of Carla Ripamonti. However, distension may be minimal in both jejunal involvement and fixed tumours extensively infiltrating the small bowel. In the presence of a high level of obstruction, such as in stomach, duodenum, or jejunum, vomiting develops early and in larger volumes. Nausea is persistent or occasionally subsides temporarily after an episode of vomiting. Continuous pain is due to a visceral mass growth compressing the intestine, intestinal distension, or hepatomegaly, while severe superimposed colic above the obstruction, in the small or large intestine, may worsen the distress. This activity is variable in intensity and site due to distension proximal to the obstruction. The initial symptoms are frequently abdominal cramps, nausea, vomiting, and abdominal distension that usually present periodically and resolve spontaneously. Dry mouth is associated with other symptoms, and is the consequence of severe dehydration and metabolic alterations, as well as pharmacological interventions such as anticholinergic drugs. No evacuation of faeces and no passing of flatus are typical features of complete obstruction. The eventual appearance of paradoxical diarrhoea results from leakage of faecal fluid from faecal impaction, generally in large bowel obstruction. Vomiting can be assessed in terms of number of episodes, volume, and overall duration. Other symptoms such as nausea, pain (both colicky and continuous), somnolence, dyspnoea, and, at times even the sensation of hunger can be present and can be evaluated with visual analogue, numerical, or verbal scales. The diagnosis of intestinal obstruction is established or suspected on clinical grounds and confirmed with abdominal radiographs demonstrating air­fluid levels. The preferred radiological procedure has evolved in recent years but it varies in different parts of the world according to the local expertise and the availability of each imaging modality. These should only be used if they are going to directly inform clinical decisions. Plain X-ray can document the air-filled dilated loops of bowel, differential air­fluid levels, or both, but the accuracy for localizing the point and cause of obstruction is low. In the face of a clearly incurable situation, significant patient discomfort and suffering must be balanced with the short life expectancy. The physicians need to consider a series of questions when faced with terminal cancer patients (patients no longer responsive to specific oncological therapies) with bowel obstruction: Is the patient fit for surgery Endoscopic stent placement cannot be done beyond the length of the endoscope, cannot be done for long obstructions, and may not be possible due to previous surgical alterations of the anatomy. Because of a perforation rate of 7­14% and a long-term failure rate of 25­30%, stents are not always the best long-term solution and surgical palliation is likely to provide more durable palliation in patients where there is likely to be a longer survival, as demonstrated in a group of ovarian cancer patients (Abecasis et al. The selection of patients who will benefit from these procedures is an ongoing challenge and can be done only by multidisciplinary teams working in close collaboration. Surgical options include complete resection, operative bypass, lysis of adhesions, the creation of a diverting stoma, whether in the small or large bowel, or a combination of these. Complete resection of an obstructing lesion is only beneficial if all tumour in that area can be resected with negative margins, and therefore is most often possible for cancers originating within the digestive tract. In a bypass procedure, if the tumour cannot be resected, but there is healthy non-obstructed bowel before and after the site of obstruction, the two healthy segments can be connected, allowing the bowel contents to go past the blockage. Diverting stomas bring the bowel out to the skin, allowing stool to empty into a bag, and effectively relieving distal obstruction. They can be made of either small or large bowel, and are created out of the most distal unaffected bowel segment. Even so, high small bowel stomas may have high outputs and may cause significant fluid balance problems (Easson, 2007). Surgical procedures An open or laparoscopic surgical procedure can successfully relieve obstruction in the appropriate patient (see also Chapter 12. Patient selection for surgery the decision to undergo a palliative procedure is facilitated if the goals and definition of success are clearly defined preoperatively. Explain clearly the expected potential benefits of any intervention: is this something that would be worth it to them given the risks Easson, Surgical Approaches to Malignant Bowel Obstruction, the Journal of Supportive Oncology, Volume 6, Number 3, pp. All treatment options including surgery, endoscopic procedures, interventional radiology, and aggressive medical management should be discussed, along with the complication rates and the expected success of each intervention. The surgeon should be prepared to make a recommendation rather than just providing information (Dunn et al. With careful preoperative planning it is possible to determine before the operation in most cases which operation is most likely to succeed; however, the final decision must be made in the operating room. The possibility that no surgical procedure may be possible should also be discussed preoperatively; the patient and family must be prepared for that option and consider advance directives or substitute decision-makers. Finally, there must be a commitment to ongoing care with a clear care plan whatever the outcome of the surgery. The number of obstructed sites also affects the likelihood of success; a single site of obstruction has a high likelihood of success when compared to multiple sites of obstruction. The selection of patients who will benefit from these procedures is an ongoing challenge. The procedure that is the most likely to successfully relieve symptoms for the greatest length of time with reasonable morbidity is chosen (Krouse et al. Performance status remains one of the best predictors of lower complication rates and improved survival (Wright et al. Disease factors such as tumour type, grade and extent, time from primary presentation, and history of response to and availability of anti-cancer treatments also affects prognosis and likelihood of success (Henry et al. Significant symptom relief can be obtained by selecting appropriate patients either for surgery or stenting with minimal procedural mortality (Imai et al. Endoscopic stenting for gastroduodenal and proximal jejunal obstruction Malignant gastric-outlet and duodenal obstruction commonly occurs from neoplastic invasion or extrinsic compression by carcinoma of the stomach, head of the pancreas, gall bladder, and bile duct or from compression by metastatic lymphadenopathy in the porta hepatis from a number of abdominal and extra-abdominal primaries. The procedure can be performed under conscious sedation, but because of the frequent presence of significant food retention in the stomach, the risk of aspiration is high, in which case general anaesthesia with airway intubation will help to minimize that risk.

A spot in the centre of the pupil pulse pressure heart ramipril 5 mg buy free shipping, looking as if it were on the surface of the lens blood pressure medication verapamil ramipril 2.5 mg buy on line, may be a pupillary exudate or an anterior polar cataract heart attack causes ramipril 2.5 mg buy without a prescription. Triangular spokes of opacity with their apices towards the centre are indicative of a cuneiform senile cataract blood pressure range for men purchase generic ramipril online. A white appearance over the whole pupillary area suggests a total or mature cataract; if it is yellowish-white blood pressure medication algorithm 10 mg ramipril buy with amex, with white spots of calcification and the iris is tremulous, a shrunken calcareous lens should be suspected. Finally, the pupil may be blocked with uveal exudates forming an inflammatory pupillary membrane. Diffuse Illumination Diffuse illumination allows an observer to obtain a direct and tangential view of the anterior segment of the eye. Diffuse illumination allows determination of general features, such as colour, size and relative position of structures. This is followed by tangential illumination with a large angle of illumination, which helps to increase contrast and highlight the texture of ocular tissues. Focal Illumination Focal illumination is used for direct observation of the illuminated point, direct focal examination, or to allow observation of an adjacent area, indirect focal viewing. This permits the observer to cut an optical section of the anterior segment at any angle. Optically the homogeneous media appear quite black; structures such as the cornea, lens and suspended particles in the aqueous scatter light and appear opalescent. A dim central interval can be distinguished, formed by the embryonic nucleus with its Y-sutures. Ocular problems can be identified by different methods of examination, which differ in the positioning of the illuminating light and the angle between the illumination and observation arms. Various permutations and combinations of these techniques are used, some simultaneously and others sequentially. Specular Reflection Specular reflection allows the observer to visualize the corneal endothelium by viewing light reflected back from this interface. The illuminating and viewing arms are adjusted so that each forms an angle of about 30° to the central perpendicular, the slit-lamp beam is narrowed to a height of 2 mm and focused onto the central corneal endothelium. This is placed immediately adjacent to the reflection of the slit-lamp bulb on the cornea. Scleral Scatter this is an indirect form of illumination, created by decentring the beam after releasing the central locking screw and directing a broad beam to the temporal limbus. This light is totally internally reflected through the thickness of the cornea, like a fibre-optic light pipe, and emerges at the opposite limbus. Retroillumination In this form of examination the illuminating and viewing arms of the slit-lamp are placed along the same axis, coaxially, or nearly the same axis, paraxially. It also highlights the presence of defects in the integrity of the normally opaque iris. The light reflected off the iris allows visualization of subtle, transparent corneal irregularities, such as ghost vessels or keratic precipitates. Subjective method: It may be done digitally in the same manner as testing for fluctuation in other parts of the body, i. Instruments known as tonometers have been devised for measuring the intraocular pressure of the intact eye and are of two types. An assistant may separate the lids while you concentrate on proper placement of the tonometer. After anesthetic drops are instilled, the patient will not experience any pain from this procedure. It is important to have a relaxed patient because squinting and blepharospasm may interfere with the reading. If the scale reading is less than 5, use the nest highest weight that will give a reading of 5 or more. Use the above chart to determine the converted reading based on the reading and the amount of weight on the scale. The depth and the volume of the indentation are dependent on the intraocular pressure and the distensibility of the ocular walls. The instrument is calibrated so that the equivalent readings in millimetres of mercury can be read off a chart. The Schiötz tonometer is often inaccurate, largely because of wide individual variations in the rigidity of the corneoscleral coats. However, the tonometer is useful for obtaining approximate readings, particularly for comparative measurements, such as between the two eyes or for successive measurements on the same eye. To allow for this inaccuracy the type of tonometer should always be cited and the reading expressed in this form 220. The readings are not accurate in steep, thick or irregular corneas, high myopia or hyperopia, with the use of miotics, vasodilators or vasoconstrictors, or after any intraocular surgery, especially vitreoretinal surgery. Instead of measuring the amount of indentation, the applanation tonometer assesses the amount of force needed to flatten or applanate a known area of the cornea. In this process, the factor of ocular rigidity is offset by an induced capillary force acting in the opposite direction. When the cornea is flattened by the application of a plane surface on it, the intraocular pressure is directly proportional to the pressure applied and inversely to the area flattened. In it, a flat circular plexiglass plate 7 mm in area is applied to the anaesthetized cornea so as to flatten an area 3. The constancy of the area of applanation is ensured by an ingenious duplicating optical device, formed by prisms placed apex to apex. The patient is seated at a slit-lamp after anaesthetizing the cornea and applying 1% fluorescein dye in the palpebral sac. The most accurate reading is obtained when the two inner edges of the mires coincide. The mires should not be too thick or too thin, because of excess or scarcity of fluorescein, as the intraocular pressure will then be over- or underestimated, respectively. In the presence of excessive corneal astigmatism two readings should be taken at right angles; the average is taken as the reading. A hand-held version is available as the Perkin tonometer, which can be used in any position. Another technique of measuring intraocular pressure using the applanation principle is that of Mackay Marg. End-point of perfect alignment of mires when recording intraocular pressure with the Goldmann applanation tonometer. The average of several tracings is taken as the reading of the intraocular pressure. A digital, hand-held version of the same is available as the Tonopen tonometer, which provides a mean and standard deviation of 4­10 acceptable readings, automatically. Non-contact tonometers also utilize the principle of applanation, a calibrated, warm puff of air is projected on the cornea and a photoelectric cell measures reflected light obtained when a fixed area of cornea is applanated. In many conditions such as glaucoma, foreign bodies or tumours, a close inspection of this region is important. It can, however, be observed by the slit-lamp provided the beam is diverted at an angle. For this purpose several types of gonioscopes have been developed, the simplest of which is the indirect gonioscope typified by that of Goldmann Table 11. Gonioscopes with one, two or four mirrors are available, of which the 4-mirror gonioscope allows the examination of 360° of the angle without rotating the lens. In a narrow angle, aqueous is displaced from the centre peripherally, to push away the iris, and allow better visualization of the angle structures. They are reflected by the mirror into the angle, and again, as they emerge, into the objectives of the slit-lamp microscope. The slit beam permits evaluation of the angle between the corneal endothelium and peripheral iris. The figure on the extreme left shows a fully open anterior chamber angle and on the extreme right a fully closed angle. Narrowing of the angle can be identified by a steep configuration of the iris and the angulation of a slit light reflex as it passes into the angle recess. The Schwalbe line can be identified by following the anterior and posterior surfaces of the corneal slit to the point where they meet. If, however, a solid mass lies in the path of the light, the beam is obstructed and the pupil remains black. For this purpose, special transilluminators may be employed or, more simply, a cap with an open hole at the end may be fitted over the bulb of an electric ophthalmoscope. Only the anterior half of the eye can be transilluminated in this way, but if there is a mass in the posterior segment of the globe, it can be transilluminated only after the capsule of Tenon has been opened and the transilluminator inserted within it. In such a case, a somewhat less reliable method is that of indirect transillumination, in which a powerful source of light is placed in the mouth illuminating the eyes from behind. Ultrasound biomicroscopy image of a trabeculectomy strikingly luminous appearance but if a solid mass occupies the fundus, they appear black. These structures are amenable to direct observation with a torch light and more detailed examination using magnifying aids such as a slit lamp biomicroscope. In case of obstruction of view by pathology, indirect observation is possible using ultrasound biomicroscopy. Modern technological advances like anterior segment optical coherence tomography, confocal microscopy and photography using a Scheimpflug camera enable the anterior segment structures to be viewed in greater detail akin to gross histopathology. Compiled by the Task Force on Undergraduate Teaching in Ophthalmology of the International Council of Ophthalmology and based on their curriculum, 2009. In ordinary circumstances the pupil looks black, and no reflex is obtained from the fundus. Reversing the direction of the rays, all rays from the illuminated spot of the retina are brought to a focus at the source of light. It follows that no rays will enter an observing eye unless it is situated at the source of light. If the eye is not focused for the source of light, the conditions are different, and some slight luminosity of the pupil may be seen. This is one cause of luminosity in the pupils of very hypermetropic eyes and in pathological conditions when the retina is displaced forwards as in detachment or by a tumour. Hence the emergent rays from the illuminated area of the fundus are divergent, as if coming from I. Therefore, an observing eye situated anywhere within the area I1 to I2 of the cone of emergent rays will catch some of them, and the pupil of the observed eye will appear feebly illuminated. In these circumstances it is not necessary for the observing eye to occupy the exact position of the source of light, but only a spot in its immediate neighbourhood. On the same principle, the extremely hypermetropic retina pushed forwards by a tumour can be seen well by focal illumination. A source of light was placed beside the observed eye and the glass plate obliquely in front of it, so that a portion of the light was reflected from the surface of the plate into the eye. On looking through the transparent plate an observer could now receive some of the rays from the fundus into his own eye, and thus obtain an image of the illuminated fundus. Since a small proportion of the light received upon the plate was reflected at its surface, the illumination was feeble. Next, von Helmholtz increased the amount of light reflected by superimposing three plane plates. The back of the glass was then converted into a more powerful mirror by silvering it, leaving a small portion, a hole in the mirror, unsilvered through which the observer might look. The illumination was still feeble, since the rays reflected by a plane mirror were divergent. Reute (1852), therefore, introduced the perforated concave mirror, which is still generally used. The final modification was the addition of a battery of small lenses of various strengths, which could be brought into position behind the aperture. The many forms of ophthalmoscopes are merely various mechanical contrivances for doing this most conveniently. Preliminary examination with the plane mirror alone at a distance of about 1 m from the patient. Examination with the mirror alone at a distance of about 22 cm from the patient or distant direct ophthalmoscopy. By (1) the nature of the refraction of the eye under examination can be known; this will prevent many difficulties when seen at closer quarters. By (2) any gross changes can be visualized, especially opacities in the refractive media; these may at once be made evident by this method, whereas they may be very puzzling if first observed by (3) or (4). By (3) we get a general view of the fundus-the largest possible area under moderate magnification; it is comparable to microscopic examination with a low power. By (4) and (5) details are examined under a high magnification; it is comparable to a microscopic examination with a high power. For examination with the plane mirror alone the observer sits facing the patient, about a metre away. The patient is asked to relax his accommodation by looking at a distant object, or a cycloplegic can be used. Light from the plane mirror is reflected into the eye, while the examiner looks through the sight-hole. There ought to be no black spots in the pupillary area, but either a uniform red reflex or obscure details of the fundus. By tilting the mirror to-and-fro in various directions the examiner can obtain an approximate idea of the refraction of the eye. The observer now approaches the patient until his eye, still with the plane mirror, is about 20 cm from the eye under observation. He can now see the cornea and iris clearly, and can confirm any points, which were noted previously by external examination.

Addition of an electron beam boost to enhance the dose to the tumour is often associated with severe local skin reactions blood pressure under 80 cheap ramipril 10 mg visa. Daily washing with mild soaps hypertension remedies buy generic ramipril 10 mg on-line, and avoiding the use of deodorants and electric razors prehypertension eyes ramipril 5 mg purchase with mastercard, may help blood pressure ranges low buy generic ramipril 5 mg on-line, and the basic care consists of ointments blood pressure medication and coenzyme q10 order cheap ramipril, creams, and lotions to moisten the skin, ease the burning sensation, restore elasticity, and prevent breakage and erosions. It is important to note that the vehicle of the beneficial preparation may be as influential in its effectiveness as the active component in it. Corticosteroid creams and ointments may reduce vasodilation and inflammation, but have no preventative effect and their advantage over non-steroidal preparations is doubtful. Oil-in-water emulsions are a good option (such as Biafine and aqueous creams), and calendula oil, sucralfate, and barrier films have been tried with favourable effects (McQuestion, 2006). Ulcers and erosions are treated with silver sulfadiazine (Silverol) and hydrophilic dressings such as Tegaderm and Vaseline gauze. Oral opioid mu-receptor antagonists (such as naltrexone and nalmefene) may be beneficial but cannot be used when an opioid analgesic is needed for pain. Topical application of naltrexone was recently reported as having anti-pruritic effects and the advantage of avoiding withdrawal (Bigliardi et al. For patients with good performance status, phototherapy using ultraviolet B spectrum is a good option (Seckin et al. Dryness and erythroderma General dryness, xerosis, is a common skin condition in cancer patients. Xerosis may follow chemotherapy administration, a period of decreased food intake, or hypoproteinaemia. Lack of elasticity of the drying skin creates cracking lines over the trunk and lower limbs, resulting in itching and soreness. It often is associated with exfoliation and is, essentially, an end stage of many skin diseases, including psoriasis and papulo-squamous disorders. It also is a clinical hallmark of Sézary syndrome, which is a rare variant of cutaneous T-cell lymphoma. In the wider oncological context, erythroderma may accompany leukaemia and lymphoma (Robak and Robak, 2007), and, less commonly, solid tumours. The mechanism is unknown and it is sometimes managed with emollients and systemic steroids. Chronic radiodermatitis Delayed damage to the skin is primarily a function of radiation effects on the vasculature. A second phase of dermal thinning tends to develop after more than 52 weeks, often accompanied by the appearance of telangiectasia (Hopewell, 1990). Radiation-induced skin necrosis and chronic ulcers may develop and persist indefinitely, especially over the scalp and leg. Trauma, chronic friction, and pressure contribute to the development of radiation ulcers. For chronic radiodermatitis, the basic treatment for intact skin consists of oil-in-water emollients and prevention of trauma. Radiation ulcers are resistant to treatment and a realistic goal would be to prevent secondary infection, pain, and fetid smell. This can be achieved with the use of hydrocolloids, but the prospects of healing are limited. Radiation-induced toxicities Radiation effects on the skin are usually divided into acute and chronic. Early effects occur during the course of radiation and the weeks thereafter, and late effects occur months and years later. The acute effects are thought to result from germinative cell failure to reproduce and replenish epidermal keratinocytes (Hopewell, 1990). Specifically, radiation destroys a section of the basal keratinocytes, stimulating non-cycling basal cells into a cycling phase; continued destruction of basal cells from ongoing radiation treatment overwhelms this process, however, and causes extensive injury. Radiation also damages dermal vasculature and leads to capillary disruption, extravasation, extracapillary cell damage, and inflammatory responses. The local release of histamine and serotonin induce vasodilation and hence erythema, oedema, and a burning sensation. Hair growth is interrupted as hair follicles revert to a resting phase and new hairs are shed. Sweat and sebaceous glands can be permanently destroyed after approximately 30 Gy in fractions of 2 Gy per day. Radiation recall Radiation recall refers to inflammatory reactions triggered by the administration of cytotoxic chemotherapy, which develop in previously irradiated areas, mainly in the skin. Typically, chemotherapy is acutely followed by a well circumscribed erythema that perfectly fits the radiation field of the past treatment. The histopathology of this area reveals mixed non-specific inflammatory infiltrate. The most common chemotherapeutic agents implicated in radiation recall are anthracyclines and taxanes. Gemcitabine, a nucleotide analogue, was implicated recently in several cases (Friedlander et al. Acute radiodermatitis Clinically, the acute phase of radiation injury can present as an acute radiodermatitis. Erythema and oedema are the first to occur, appearing after 1­2 weeks of treatment and peaking around week 3­4. Dry desquamation and moist desquamation then ensue, and in severe cases erosions, and even ulcers, may develop and be associated with severe pain. If treatment is necessary, corticosteroids or the use of non-steroidal anti-inflammatory agents may help (Azria et al. Skin toxicities of chemotherapeutic agents the skin, hair, nails, and mucous membranes are composed of rapidly dividing cells and are therefore a natural target for toxicities and adverse effects of anti-cancer drugs. New molecular targeting therapies and monoclonal antibodies now comprise a larger part in the arsenal of anti-neoplastic drugs. Alongside new indications and combinations of these drugs, novel toxicities also appeared, including skin toxicity. Paraneoplastic syndromes with skin manifestations Paraneoplastic syndrome refers to a pathological state generated by cancer in an organ or system that is not directly affected by tumour. The syndromes may be due to the production, by the tumour or by the host, of substances that directly or indirectly cause disease, or by depletion of essential substances. There is a variety of paraneoplastic syndromes involving the skin and these skin manifestations can precede or follow the diagnosis of cancer, indicate a recurrence of disease, or have no correlation with the course of the neoplasm. In the patient with advanced illness, the discomfort caused by skin manifestations is often overshadowed by the neoplastic disease itself. It has been associated with almost every type of solid tumour, including ovarian, pancreatic, lung, stomach, or colorectal (Hill et al. Among adults older than 40 years who have melanoma or lymphoma, the disorder is especially common, affecting 15­50% of patients (Braverman, 2002). The heliotrope is a violaceous rash with or without oedema involving periorbital skin. Other characteristic features include a slight scale and, on some occasions, a thick psoriasiform scale; telangiectasia; an erythematous eruption in a photosensitive distribution; and periungual changes. Electrophysiological or laboratory evidence of myopathy, including elevations of creatine kinase, aldolase, lactic dehydrogenase, or alanine aminotransferase, are supportive. An evaluation of malignancy should be considered in all adult patients with a consistent syndrome (Callen, 1982). In resistant cases, immunosuppressive agents, such as methotrexate, azathioprine, cyclophosphamide, mycophenolate mofetil, chlorambucil or ciclosporin, may be helpful in inducing remission. Skin pathology may be ameliorated by topical steroids or topical immunosuppressants, such as 0. Common adverse effects of chemotherapeutic agents the potential effects of conventional chemotherapeutic agents are extremely diverse. Multiple syndromes have been defined and there is large inter-individual variation in presentation and severity. Alopecia the rapidly dividing and proliferating cells of hair follicles are targeted by many chemotherapies, and the resultant alopecia is one of the most common and distressing side effects of these drugs. Scalp hair is affected to a larger extent than the slowly growing eyelashes, eyebrows, and body hair. Mucositis Mucositis includes damage to mucous membranes, most frequently of the oral cavity, and is characterized by redness, swelling, white exudates, and in severe cases, ulceration. In severe cases, the patient may not be able to drink water due to distressing pain. Almost all anti-neoplastic agents are associated with mucositis, but the severity is dependent on patient-related factors, the specific drugs employed in treatment, and varied comorbidities. Patient susceptibility to mucositis may be genetically determined, perhaps related to the expression levels of pro-apoptotic and anti-apoptotic genes (Sonis et al. Other drugs with high rates of mucositis include methotrexate, cytarabine, and taxanes. Myeloablative conditioning prior to stem cell transplantation may cause severe stomatitis. The severity of mucositis may be greatly worsened by the occurrence of mucosal candidiasis secondary to reduced immunity. Superimposed herpes simplex infection also may severely complicate chemotherapy-induced stomatitis; extensive erosive components and circumscribed ulcers should raise the suspicion of herpes simplex virus infection. Daily chlorhexidine mouthwash is often recommended as a preventative, but its efficacy is doubtful. Brittle hair, fingernails, and toenails develop and premature greying of hair may occur. Mucosal involvement by lichenoid eruption causes food sensitivity and in severe cases can develop to ulceration, especially at the biting line. Antimicrobial agents against complicating herpes simplex infection also may be required. Systemic administration of granulocyte macrophage colony-stimulating factor apparently reduces the development of radiation- and chemotherapy-related mucositis (Stokman et al. Palifermin (recombinant human keratinocyte growth factor) was recently shown to decrease the severity and duration of oral mucosal injury induced by intensive chemotherapy for haematological malignancies (Spielberger et al. Nail changes and paronychia Although less commonly encountered than alopecia and mucositis, nail changes can significantly interfere with manual activities and locomotion, due to their sensitive locations. Taxanes, especially docetaxel, are the major offenders, and cause nail abnormalities in 30­40% of patients (Hussain et al. Discoloration, nail bed bleeding, and detachment of the corny material from the nail plate (onycholysis) may occur (Nicolopoulos and Howard 2002). The development of onycholysis seems to be unrelated to the drug dose or frequency of administration. In some cases, purulent exudates may accumulate beneath the nail and soft tissue swelling of the nail bed ensues. There is a tendency for nail changes to resolve gradually over weeks, despite continued treatment (Flory et al. Nail changes may be partly reduced by soaking the tips of the fingers in ice water. Topical disinfectants like povidone iodine and 6% peroxide, and topical antibiotics can reduce secondary bacterial infection. Hand­foot syndrome Also known as toxic acral erythema and palmar­plantar erythrodysaesthesia syndrome, hand­foot syndrome is a common skin reaction among patients treated with conventional chemotherapy. The earliest sign is painful erythema of the palms, soles, and fingers that later becomes oedematous, changes colour to violet, then dries off and desquamates. In severe cases, blisters develop, later leaving erosive surfaces, with considerable impairment in function. Hand­foot syndrome is often a dose-limiting toxic effect, especially for liposomal doxorubicin. Skin toxicities of molecular targeted therapies the newer molecular targeted therapies have greatly expanded treatment options for diverse types of cancer. Yet others act by competing with adenosine triphosphate binding at the tyrosine kinase site. Skin eruptions are the most common and sometimes distressing side effect of this category of drugs. Studies indicate that 45­100% of patients experience some type of cutaneous side effect (Perez-Soler and Saltz, 2005; Shepherd et al. The characteristic rash is composed of acneiform pustules on a background of seborrheic dermatitis-like erythematous plaques with oily scales. The typical distribution is on the face, upper chest and back, and less often the scalp. The rash begins during the first week of treatment and may vary in severity with repeated treatments, tending to increase initially and then partially decrease. A correlation between the clinical response to the drug and the presence of skin rash has been observed (Saltz et al. The latter condition can lead to follicular rupture and suppurative superficial folliculitis. Instead, much of the literature contains prevention and treatment recommendations based on case reports or studies with small samples sizes and nonrandomized patient allocation. Hydrocortisone 1% combined with moisturizer, sunscreen, and doxycycline 100 mg twice daily recommended for the first 6 weeks of therapy, based on data from randomized clinical trials. Oil-free moisturizing creams are used to relieve dryness and itching, and in severe cases, antihistamines can ameliorate pruritus. Dose reduction should be considered in non-remitting, severe skin symptoms (Lynch et al. Removal of pre-existing calluses and keratotic skin is recommended prior to initiation with sorafenib or sunitinib. Other preventive recommendations include orthotic devices to normalize weight-bearing and prevent friction, avoidance of friction and trauma to the hands and feet, especially during the first 2­4 weeks of treatment, and thick cotton socks and gloves to protect the hands and feet. For hyperkeratotic areas, agents that decrease keratinocyte proliferation can be used, including urea 20­40% cream, tazarotene 0. Topical 2% lidocaine can help with pain, as can systemic medications, such as non-steroidal anti-inflammatory drugs, opioids, and perhaps pregabalin (Lacouture et al.

Organ and tissue donation is an integral part of end-of-life decisions and is grounded in respect for individuals and families prehypertension caffeine discount ramipril express, respectful communication and decision-making blood pressure medication metoprolol 2.5 mg ramipril with visa, and compassionate care (Williams et al blood pressure taking cheap ramipril 5 mg buy line. The high prevalence of post-traumatic stress disorder among survivors is indirect evidence of the severity of trauma involved for many patients (Davydow et al prehypertension home remedies order ramipril 5 mg. End-of-life decisions are stressful and monumental in the lives of those involved (Kesselring et al blood pressure ranges pediatrics discount 5 mg ramipril visa. Dealing with conflicts in intensive care Conflicts regarding end-of-life decisions between families and health-care providers (Breen et al. The most common types of conflicts arise around decisions regarding whether to withdraw or withhold treatment (Studdert et al. Meetings to try to resolve conflicts should start by focusing on the common goals of caring for the patient and the family. Many intensive care services work closely with bioethicists and social workers who may be invaluable in helping resolve conflicts (Schneiderman, 2006). Conflicts between staff regarding issues of over treatment or premature forgoing of treatment are very common and are a major cause of moral distress and burnout among intensive care staff (Hamric and Blackhall, 2006; McAndrew et al. This underscores the importance of collegiality and interdisciplinary involvement in critical decision-making in which the opinions of all relevant staff members are respectfully considered (see Chapter 14. Despite this only a minority of patients receive adequate pain therapy for these procedures (Payen et al. Minimizing pain with pre-emptive analgesia or avoiding iatrogenic sources of pain should be part of the pain relief plan. Management of patient pain and discomfort with analgesia first, before resorting to sedative therapy, results in improved patient outcomes compared to standard sedative-hypnotic regimens (Devabhakthuni et al. Additionally physical movement, immobility, and increased muscle tone may indicate the presence of pain. Tearing and diaphoresis in the sedated paralysed and ventilated patient represents autonomic responses to discomfort (Herr et al. Based on these observations, standardized pain scoring systems based on physiologic variables and behavioural observations have been developed. Agitation Patients in intensive care commonly experience agitation and anxiety and the presence of these symptoms are associated with worse clinical outcomes (Atkins et al. Agitation is an undifferentiated clinical symptom and it may be provoked by multiple mechanisms including pain, delirium, hypoxemia, hypoglycaemia, hypotension, or withdrawal from alcohol and other drugs. Before resorting to sedative medications, steps to reduce anxiety and agitation should be undertaken including optimization of patient comfort, administration of adequate analgesia, frequent reorientation, and adjustment of the environment to maintain normal sleep patterns. When necessary, sedation should be titrated to maintain a light rather than a deep level of sedation, unless clinically contraindicated. However, among those patients who are delirious, sedated, or paralysed evaluations are notoriously difficult (Hawryluck et al. There is very limited direct data on the prevalence and severity of symptoms in intensive care. What data are available highlight the prevalence of pain, dyspnoea, thirst, nausea, hunger, tiredness, 15. Evaluation of respiratory distress among non-verbal ventilated patients is challenging and is dependent on recognition of behavioural indicators of respiratory distress which include (in descending frequency) tachypnoea and tachycardia, a fearful facial expression, accessory muscle use, paradoxical breathing (diaphragmatic), and nasal flaring (Campbell, 2007). Patients undergoing mechanical ventilation generally need some degree of sedation in order to maintain a modicum of comfort. This is usually achieved with propofol or dexmedetomidine (Anger, 2013; Barr et al. Benzodiazepine medications such as midazolam, while commonly used, are not preferred since they are associated with, more prolonged duration of mechanical ventilation, and higher incidences of delirium and cognitive dysfunction (Barr et al. Intravenous opioids and sedatives allow the assumption of greater control of respiratory function with mechanical ventilation, and to decrease the discomforts inherent in being on life support. Intermittent bolus doses of medications are used to supplement the infusions in anticipation of and in response to interventions that would be expected to increase pain and suffering. The use of continuous infusions results in better pain control and lower total doses of medication overall, yet many patients do require moderate to high doses of opioids and sedatives. Patients who do not require ventilation will often require symptomatic therapy for dyspnoea including oxygen and systemic opioids (see Chapter 8. The use of haloperidol, while common, is contentious and is not well founded in evidence. Data suggests that dexmedetomidine may be the preferred option for delirium unrelated to drug or alcohol withdrawal (Anger, 2013; Barr et al. This almost always involves decisions regarding the withdrawal (discontinuation) of life support or not starting life support measures (see Chapter 5. In most situations, the recognition that the patient will not survive occurs relatively quickly, most often in less than 4 days (Sprung et al. Both changing goals and making decisions to withhold/withdraw life-support are difficult for all involved, and implementing them requires planning skill and a high level of clinical vigilance and compassion. Preparing the family members Family preparation begins with discussions such as those described above (Truog et al. Clinicians must assist families through both the transition in goals and the dying process of the patient. Families need detailed explanations about the steps that will be taken to ensure patient comfort, and should also be prepared for the physical changes their loved one will likely undergo. The anticipated changes in respiratory pattern should be described as a normal part of the dying process. Clinicians should offer families the opportunity to spend more time with their loved one prior to withdrawal of life support and, if need be, to meet with a spiritual carer. As with other symptoms, it is often overlooked or misdiagnosed because of the difficulty of assessing mental states in intubated patients. As an initial step, patients should be evaluated for distressing symptoms, such as pain or dyspnoea, which may contribute to delirium, and if identified these ought to be addressed. It is important to start communicating this possibility a day or two before it is necessary. This transfer should occur smoothly with deference to the needs of the patient and family. Every effort should be taken to reassure family members that continuity of clinical and especially comfort care will be maintained. While this is accepted practice in some places (Billings, 2012), it is not universal and some argue that this is a modified version of physician-assisted death (Rady and Verheijde, 2010; Carvalho et al. Comfort measures Ensure availability of analgesics and sedatives to rapidly treat distress. This should include infusions of opioids and sedatives, as well as bolus doses of rapidly acting agents to manage distress. Discontinue interventions that are not consistent with the goals of care All routine interventions that provide no comfort to the patient. All therapies should be re-evaluated and those that do not contribute to patient comfort should be discontinued. Unless there are specific objections by family members, electronic monitoring should generally be discontinued as it does not provide comfort and it may distract the family from care of the patient and of one another (Rubenfeld, 2004; Truog et al. Discontinuation of vasopressors, inotropes, and antibiotics results in no discomfort and they do not need to be weaned (Truog et al. When a patient has specifically refused one form of lifesustaining treatment on the basis of personal values. In general, these wishes should be followed as long as they are consistent with good quality care and they do not compromise the care of other patients. Discontinuing ventilation support Ventilator support is gradually withdrawn by decreasing the fraction of inspired oxygen and the amount of positive pressure ventilation over a period of 10­30 minutes in a way that allows the patient to comfortably transition to spontaneous breathing on room air through the endotracheal tube. The patient is assessed for signs of distress after each reduction in support and additional boluses of intravenous analgesics or sedatives should be administered as needed. Extubation at the end of life is a complex decision that defies dogmatic approaches and agreement should be achieved between staff and the patients surrogate decision-makers regarding this issue. While some clinicians suggest extubating the patient to free the patient from unnecessary lines and tubes prior to death, and to facilitate a more natural appearance during the dying process this may not always be prudent. Patients who are extubated after receiving high levels of ventilator support, and those with difficulty clearing secretions or protecting their airway, often become distressed with struggling and gasping (Prendergast and Puntillo, 2002). Indeed, in many situations, especially when upper airway collapse is anticipated, it is acceptable to leave the endotracheal tube in place. Discontinuing mechanical ventilation is often very difficult, and sometimes traumatic for clinicians and families alike. The goal is to discontinue ventilation in a manner compatible with staff and family sensitivities and at the same time to assure patient comfort during all phases of the procedure. Well-tested protocols have been developed and published to facilitate safe and effective approaches to withdrawing mechanical ventilation (Treece et al. Among the principal considerations are the following key elements: Continuing care Patients should be cared for in a clinical setting that allows for monitoring of symptoms and the ability to treat them effectively. Discontinue neuromuscular blockade Neuromuscular blockade may mask patient distress and confound the physical assessment of stress (Brody et al. Neuromuscular blockade should be discontinued before withdrawal of life support either by allowing the paralytic agent to wear off or by pharmacologically reversing its effects. In the rare cases in which it is felt that waiting for the return of neuromuscular function would be excessively burdensome, deep sedation should be established before withdrawal of therapies (Truog et al. At the bedside of the imminently dying patient Whenever possible, a member of the health-care provider team should offer to be available to be with the family as the patient is dying. In so doing, the health-care professional can defuse some of the strangeness of the situation for the family, and make it somehow more of a normal and natural process (as indeed it is). When possible, encourage family participation in patient care (Prendergast and Puntillo, 2002). This promotes a sense of comfort, intimacy, and involvement when families are in an otherwise strange and tragic and, sometimes, impersonal situation. Family members can be encouraged to communicate with their loved one through speech, touch, song, prayer, or music. Caregiving activities can include assisting with face washing or hair combing, or gentle massage. For some family members, however, being present as the patient is dying is overwhelming and respect for emotional limits is itself a caring practice. The role of the clinician at the bedside of the dying patient is to ensure adequate relief of patient distress and to provide support Pre-emptive sedation Many patients may need pre-emptive dosing of opioids and sedatives to prevent any sudden increase in dyspnoea which may occur even if the patient has been gradually weaned from ventilator support (Billings, 2012). There is wide interindividual variability for dosing requirements and, for some patients required doses may be high (Brody et al. Sedation should be administered continually with provision for bolus rescue doses as needed (Brody et al. The physician should evaluate the patient to ensure that the patient is comfortable. If present, pain, dyspnoea, agitation, or any other distressing symptoms that are remediable should be rapidly and effectively treated. Once adequate comfort is achieved, the physician should reassure the family that the patient is not in distress. Families vary in the degree of professional support necessary at the bedside of the dying. Attentive and continual presence is often needed when family supports are limited or coping is frail. In other situations it may be more appropriate for the clinician to acknowledge the primacy of family and friends in this setting and to take a background position of availability if necessary. If it is clear that breaths are agonal and the patient is about to die, it is often appropriate to indicate this to the family with the reassurance that the patient appears comfortable. The clinician should indicate that death has occurred when there are no signs of life and offer support and condolences. Adequate provision for time and privacy in this situation is strongly recommended. This model focuses on interventions to increase staff awareness of patient/family palliative care needs, improve communication skills, and incorporate palliative care skills training in staff education. Education Although there is a wide consensus that end-of-life care is a critical skill for intensive care clinicians, there are no uniform widely endorsed guidelines for the training of intensive care clinicians in palliative and end-of-life care and evidence suggests that the scope of actual training is variable (Kane et al. Detailed curriculum guidance was developed by a multidisciplinary taskforce including intensive care specialists, palliative care specialists, ethicists, and consumer advocates (Danis et al. This very comprehensive document highlighted nine attitudes and skills critical for good palliative care performance by intensive care clinicians: appreciating the patient as a person; communicating effectively by listening well to patients and their families; being able to deal with prognostic uncertainty; being comfortable broaching the topic of death with patients and their families, and supporting them in facing this reality; negotiating the overall goals of care; switching from the simultaneous provision of life-supporting therapy and comfort care to comfort care only; providing excellent palliative care; giving explanations, ranging from small details to the large picture, in clear, understandable language; and working effectively in collaboration with a multidisciplinary health-care team. The American Association of Colleges of Nursing have developed a comprehensive modular training programme for end-of-life care specifically designed for nurses working in intensive care (Ferrell et al. After a patient death the death of a patient stresses the physical and emotional resources of the professional health-care providers as well as the grieving family and friends. This process can be facilitated by expressions of mutual support and appreciation, and debriefing sessions in which the care of the patient is reviewed. These tend to occur when the patient, family, and staff experience conflicts around goals and methods of care. Proactive ethics consultations for patients at high risk of dying, have also demonstrated similar benefits, including reduced conflict among the staff members and between staff and family members (Schneiderman et al. Representation of both physicians and nurses is essential, and involvement of staff educators and other disciplines such as social work, psychology, and chaplaincy is preferred. This step should be completed before the development of strategies to improve care. Conclusions Intensive care patients have high degrees of morbidity and a relatively high risk of mortality. Under these circumstances, quality care demands a high level of skill in the core palliative care competencies, including communication, symptom control, goal setting, and end-of-life care. The particularities of the intensive care setting alter the context of discussions and decision-making and the particular issues relating to the foregoing of life-sustaining interventions as part of end-of-life care. The right of patients to adequate relief of unpleasant symptoms at the end of life and the right of family members to compassionate care imply duties incumbent upon individual clinicians working in this setting as well as on the organizational structures to ensure adequate levels of skill, compassion, and organization to meet the challenging needs of intensive care patients and their families.

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