By S. Candela. Drake University. 2019.

The first day of the fertile period is cal- involves laparotomy discount quetiapine 200 mg with visa, does not always work (microsurgical culated as the length of the shortest cycle minus 20 days quetiapine 50 mg on line, techniques have around 70% success) and carries a signifi- and the last day of the fertile period as the longest cycle cant risk of ectopic pregnancy (up to 5%) effective quetiapine 300mg. Therefore if cycle length varies from 25 to lization with micro‐inserts cannot be achieved via fallopian 30 days quetiapine 100mg low price, the potential fertile period and days when inter- tube re‐anastomosis, and therefore consideration should course should be avoided are days 5–20. Contraception and Sterilization 951 the mucus or Billings method relies on identifying management of a medical problem the risk–benefit ratio changes in the quantity and quality of cervical and changes. As circulating oestrogens increase with heavy menstrual bleeding and more cost‐effective than follicle growth, the mucus becomes clear and stretchy other medical therapies and endometrial ablation. With ovulation, and in the reduces the pain of endometriosis and adenomyosis and presence of progesterone, mucus becomes opaque, sticky protects against unopposed oestrogen. Persona may be used by women to detect the fertile toms of endometriosis and, given the high incidence of phase of the cycle); the monitor displays a green light for amenorrhoea, is also used for heavy menstrual bleeding. Whatever method is used, many couples retically also protect against ovarian cancer. Conclusion Lactational amenorrhoea method Obstetricians and gynaecologists often underestimate Breastfeeding delays the resumption of fertility after a woman’s need for immediate effective contraception. A woman who is fully or nearly fully breastfeeding and Immediately after pregnancy is a key time to provide who remains amenorrhoeic has less than a 2% chance of contraception, since fertility and sexual intercourse pregnancy during the first 6 months after childbirth resume quickly. Hormonal methods of contraception Non‐contraceptive benefits can effectively manage a range of gynaecological con- of contraception ditions. It is essential therefore that obstetricians and gynaecologists can give high‐quality information to Hormonal methods of contraception in particular have women about the range of contraceptive methods and many non‐contraceptive benefits. Interpregnancy interval 19 Faculty of Sexual and Reproductive Healthcare Clinical and risk of preterm birth and neonatal death: Effectiveness Unit. Immediate post‐partum insertion of 9 Faculty of Sexual and Reproductive Healthcare. Cochrane Database Syst Rev Medical Eligibility Criteria for Contraceptive Use 2016. A pilot 24 Faculty of Sexual and Reproductive Healthcare Clinical randomised study. Improving the uptake of long documents/cec‐ceu‐guidance‐implants‐feb‐2014/ acting reversible contraception: a review. Copper containing, framed intra‐ 26 Faculty of Sexual and Reproductive Healthcare Clinical uterine devices for contraception. Progestogen‐only women who acquire pelvic inflammatory disease: a contraceptive use in obese women. Obstet Gynecol thromboembolic events in women taking progestin‐ 2013;122:1205–1213. Clinical guidance: Emergency users: cohort evidence from Royal College of General contraception. Clinical guidance: Male guidance/documents/fsrhstatementvteandhormonalco and female sterilisation. Breast cancer and hormonal contraceptives: a 42 Faculty of Sexual and Reproductive Healthcare Clinical collaborative reanalysis of individual data on 53,297 Effectiveness Unit. Clinical guidance: Fertility women with breast cancer and 100,239 women without awareness methods. In the most recent survey of individuals ‘any sexual behaviour – normal and abnormal, mastur- aged 16–74 years who lived in Britain (England, Scotland batory and partnered – rests upon biological elements, and Wales) that was completed between 2010 and 2012, psychological elements, interpersonal elements, and cul- data were available for 6777 women (and 4913 men) [2]. Low sexual function was also associated quality of life has been emphasized by greater numbers of with experiencing the end of a relationship, an inability women approaching gynaecologists and other clinicians to talk easily about sex with a partner and not being seeking help for sexual (and often relationship) problems. Associations were also noted Alongside this is an expectation to be able to raise the mat- with engaging in fewer than four sex acts in the preced- ter with their healthcare professional without fear of rejec- ing 4 weeks, having had same‐sex partners and having 10 tion or embarrassment. Provision of clinical services for the emerging women in a sexual relationship for the past year, 27. Trends were reviewed over the three decades that the surveys have taken place (Natsal 1, 1990–1991; Natsal 2, 1999–2001; Natsal 3, 2010–2012). The percentage of women who thought that one‐night stands were ‘not wrong at all’ increased ● Sexual activities offer both reproductive and pleasur- from 5. The percentage of women thinking that female ● Healthcare professionals should offer women the same‐sex partnerships were ‘not wrong at all’ increased opportunity to discuss any areas of concern about from 27. The authors conclude in their review that sex- ● Sexual medicine is a multidisciplinary field of medicine ual lifestyles in Britain have changed substantially in the incorporating gynaecology, psychology and couples’ past 60 years, with changes in behaviour seemingly psychotherapy. The continuation of sexual Dewhurst’s Textbook of Obstetrics & Gynaecology, Ninth Edition. The most common problems reported were lack the aetiology of unhappiness within a relationship is of sexual interest (34%) and lack of pleasure in sex (25%). Talking to their partner was the most common amongst many issues, their ways of connecting, commu- action taken by women (32. Other key areas may had been asked by a doctor about possible sexual diffi- include dealing with issues of power and trust within a culties during a routine visit in the previous 3 years yet relationship. More recently, an intimacy‐ identified that over 98% of women reported one or more based model of a women’s sexual response cycle was sexual concerns that often changed as women aged but introduced by a team of experts. This model that most of the women had not had the topic of sexual reflects the key roles of emotional intimacy and sexual health ever raised by their physicians [5]. The clinic envi- stimuli, unlike the earlier models which tended to ronment may not be conducive to routine enquiry but neglect the importance of emotional intimacy as a moti- this should be addressed by changes to the patient clinic vator to find or be responsive to sexual stimuli. However, there are additional models that ● Sexual problems are common within the community may be important when considering sexual function and but persistent problems for over 6 months are much dysfunction and the interested reader is referred to a more unusual. These are lust (sex drive, libido), driven by androgens; attraction (passionate (A) romantic love), driven by dopamine; and attachment A B C (C) (bonding), driven by oxytocin [6,7]. Emotional and Physical Satisfaction Spontaneous Sexual Drive Sexual Stimull Arousal and Sexual Desire Sexual Arousal Sexual response: anatomy problems may be the presenting symptom for significant and physiology underlying disease, the argument for mandatory aware- ness and training in the field is increasing [12]. The anatomy and physiology of sexual function and dys- Vaginal lubrication comprises vaginal transudate, function is not always overtly taught at medical school or often with secretions from the Bartholin’s glands and the in postgraduate courses, with several obstacles prevent- paraurethral Skene’s glands. The process of transudation ing sexual health from being adequately addressed in depends on both intact innervation and normal oestro- health professionals’ curriculum. The process of parasympathetic activation via ority given to the topic and a lack of standardized objec- the sacral nerves S2–S4 leads to an increase in vaginal tives and means for evaluating any current curriculum. It has been shown that the process of vaso- Given the raised awareness that medical conditions can motion occurs with the random opening and closing of result in sexual dysfunction and the fact that sexual the capillaries of the vaginal wall. Sexual Dysfunction 957 low basal flow is maintained by both high sympathetic phalloplasty, a gynaecologist may be approached, with (T12–L2) inhibitory tone and vasomotion [13]. Some women may an increase in the blood flow to the clitoris, an organ present to gynaecologists having transitioned from a which is much hidden from routine inspection of the male gender role. The perineal urethra is embedded in the anterior offered the same clinical care as any women whilst rec- vaginal wall and is surrounded by erectile tissue in all ognizing there will be some differences in clinical needs directions, except posterior where it relates to the vagi- during the post‐perioperative care period and in the nal wall [14]. The clitoris and where necessary, liaison with the surgeon involved appears to exist solely for the purpose of sexual pleasure.

Mesenteric Arteriography Because a more rapid bleeding rate is necessary for a positive arteriogram (0 generic quetiapine 100mg line. However buy generic quetiapine 300 mg line, because of the intermittent nature of bleeding and the variable timing of mesenteric arteriography purchase quetiapine 300 mg amex, a positive red blood cell scan does not always result in a diagnostic arteriogram [8] purchase quetiapine 100mg amex. Intravenous proton pump inhibitors, administered either as intermittent bolus doses or continuous infusion, decrease risk of rebleeding, need for surgery, and death in peptic ulcer bleeding [108–110,112]. Endotherapy is indicated for all patients with high-risk lesions because of the significant risk of persistent or recurrent bleeding (22% to 55%) and even death if left untreated [3,4,46]. However, vigorous lavage of adherent clot can uncover stigmata requiring endoscopic treatment in nearly half of patients and can be performed at the discretion of the endoscopist [11]. The most common modalities of endoscopic therapy used are thermal therapy (heater probe, bipolar probe, argon plasma coagulation), injection therapy (epinephrine, hypertonic saline, sclerosing solutions), and mechanical therapy (hemoclips, endoloops, and band ligation). Newer endoscopic techniques, including over-the-scope clips, endoscopic suturing, mucosal ablation devices, fibrin glue injection, hemostatic spray, and endoscopic ultrasound-guided angiotherapy, may improve success rates in treatment of high-risk lesions [51]. The treatment modalities are generally comparable with respect to efficacy and safety even when used in combination [3]. The Baylor bleeding score, using patient age, number of illnesses, illness severity, site of bleeding, and stigmata of bleeding, has been proposed to predict the likelihood of rebleeding [54] and may be useful in determining which patients may benefit from second-look endoscopy [30]. Angiotherapy Intra-arterial vasopressin and/or embolization are used for angiographic control of various bleeding lesions [8,55]. A recent randomized study comparing urgent colonoscopy to radionuclide scanning followed by angiography demonstrated no differences in hospital stay and transfusion requirements despite the fact that colonoscopy identified a definitive bleeding source more often. However, this study used only vasopressin infusion and did not use embolization as a mode of angiotherapy [56]. Gelfoam and metal coils used for embolic therapy after superselective cannulation of the bleeding artery are effective because they can be delivered close to the terminal bleeding vessel and result in localized thrombosis with vessel occlusion. Embolization successfully controls bleeding in 52% to 94% of patients, with approximately 10% of these patients requiring repeat embolization for recurrent bleeding [57]. There is a risk of bowel ischemia following embolization, but this is usually minor and self- limited [55]. Angiotherapy can be comparable to surgical intervention when endoscopic therapy fails for bleeding peptic ulcers. A retrospective analysis demonstrated no difference between embolization and surgery in recurrent bleeding (29. The timing for the use of angiography and angiotherapy must be individualized and usually is a consensus decision by the involved physicians. Surgical Therapy the appropriate timing of when a surgeon should be involved in the care of a bleeding patient is physician and institution dependent, and ranges from an early team approach at presentation to involvement once the risk of significant morbidity and mortality are established after a poor response to medical and endoscopic therapy. Surgical intervention is an effective and safe alternative for patients with uncontrollable bleeding or those unable to tolerate additional bleeding [59]. Prior to surgical intervention, a repeat endoscopy for a patient with persistent or recurrent bleeding can be considered owing to lower risks of side effects from endoscopy compared to surgery [60,61]. A possible exception may be ulcers >2 cm in hypotensive patients where the risk of rebleeding is extremely high with repeat endoscopic therapy [26,61]. Patients with massive hemorrhage that overwhelms the resuscitation effort may need to proceed directly to the surgical suite during ongoing resuscitation. If these patients are high-risk surgical candidates, angiotherapy or a percutaneously or surgically placed portal-hepatic shunt for variceal bleeding may be alternatives. Bleeding from gastroesophageal varices characteristically is brisk and typically presents as hematemesis, melena, or hematochezia in association with hemodynamic instability. The presentation may be less dramatic because acute blood loss can be self- limited in 50% to 60% of cases [62]. Once active bleeding stops, the likelihood of recurrent variceal hemorrhage is 40% within 72 hours and 60% within 10 days if no definitive treatment is pursued [48]. Risk factors associated with variceal rupture include a portal pressure gradient greater than 12 mm Hg, large variceal size (greater than 5 mm), and progressive hepatic dysfunction [66]. Endoscopic findings that implicate esophageal or gastric varices as the bleeding source include the red sign, where one varix is brighter red than the others from microtelangiectasia (red-sign variants include red- wale marks, cherry-red spots, hematocystic spots, and diffuse redness of varix), and the white-nipple sign, in which a fresh fibrin clot may be seen protruding from a varix [66,67]. Endotracheal intubation protects the airway from aspiration of blood in obtunded patients, especially in the setting of massive bleeding [68]. Additional complications that must be addressed include alcohol withdrawal, aspiration, infection, and electrolyte imbalances. Octreotide is a somatostatin analog that decreases splanchnic blood flow and portal pressure, controlling variceal bleeding in as many as 85% of patients [69,70] with an efficacy approaching that of endoscopic therapy and providing improved visibility during subsequent endoscopy [70–72]. Aside from transient nausea and abdominal pain with bolus doses, significant adverse effects from octreotide are rare. Vasopressin, once widely used in this setting, has a significant cardiovascular side effect profile and for this reason has been replaced by octreotide. Endoscopic evaluation should be performed urgently (within 12 hours) in patients in whom variceal bleeding is suspected [79]. Endoscopic band ligation has gained acceptance as the preferred endoscopic treatment for patients with bleeding esophageal varices, with rapid obliteration of varices, and low rates of complications and rebleeding (Table 203. Endoscopic variceal sclerotherapy (injecting a sclerosing solution into the variceal lumen or into the adjacent submucosa), although successful in controlling variceal bleeding, is associated with a 20% to 40% incidence of complications, and has largely been relegated to a second-line therapeutic modality, reserved for patients in whom band ligation is technically difficult [66,81]. Complications of band ligation include recurrent bleeding from treatment-induced esophageal ulcers, stricture formation, esophageal perforation, and acceleration of portal hypertensive gastropathy [82]. Repeat variceal band ligation is performed until varices are obliterated because this approach reduces the incidence of rebleeding [66]. Appropriate interval for repeat band ligation is controversial, with recommendations ranging from 1 to 8 weeks [79]. Gastric varices are detected in approximately 20% of patients with portal hypertension, but can also occur from splenic vein thrombosis. Gastric varices bleed less often, but blood loss can be more substantial compared to esophageal varices [83]. Complications include a propensity for embolic phenomenon posttreatment, including massive pulmonary embolism [85]. Embolization of the short gastric veins and varices is a potential management option for isolated gastric varices. Complications include transient deterioration of liver function, new or worsened hepatic encephalopathy (25%), and shunt insufficiency from thrombosis or stenosis [86]. When placed in an emergency setting to control active bleeding, a 10% in-hospital mortality and 40% 30-day mortality have been reported [86,88,89]. This technique requires a natural gastrorenal or gastrophrenic shunt, which occur in 95% of cases of gastric varices [90]. A balloon catheter is used to occlude the shunt, following which a sclerosant, for example, ethanolamine is injected into the varix [90]. A recent meta-analysis found a pooled clinical success rate of 97% with a major complication rate of 2. Surgically created shunts reliably control acute bleeding (>90%) and prevent rebleeding (<10%) [92,93] but are limited by high operative mortality and postprocedure encephalopathy. Therefore, surgical shunts are only considered in well-compensated cirrhotic patients with good long-term prognoses [93].

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The peroneal division of the sciatic nerve is more commonly affected than the tibial division [155]; it has been postulated that this has to do with more points at which the peroneal nerves are tethered down the lower extremity than the tibial nerves order 300 mg quetiapine otc. Prognosis of these cheap quetiapine 50mg line, however buy discount quetiapine 200mg, is poorer than that for radial nerve palsy buy cheap quetiapine 200mg online, perhaps secondary to the long distance across which recovery must occur (the nerve bud must travel from the pelvis to at least the superior leg, where innervation of the peroneal muscles and ankle and toe dorsiflexors occurs) [155]. Electromyography and nerve conduction studies are useful for characterizing the injury, and many patients with mild injuries regain good function [156]. Scapulothoracic dissociation, likened to a closed forequarter amputation [157], occurs when the shoulder girdle and upper extremity are pulled away from the midline [158]. Significant degrees of scapulothoracic dissociation can result in the rupture of subclavian or axillary vessels [157,159]. The injury complex can have devastating effects upon the neurological function of the upper extremity, due to the stretch of nerves or brachial plexus, or due to the avulsion of nerve roots from the cervical spine [157]. Degree of neurological injury and prognosis for recovery correlates with the location of vascular injury; more proximal vascular injury correlates with more severe neurological compromise and poorer prognosis [160]. Evidence of expanding hematoma within the axilla of a patient with such an injury should prompt emergent vascular surgical consultation. Careful attention to the vascular status of the distal upper extremity must be paid to any patient with a distracted clavicular fracture, a significantly displaced scapular fracture, or a clear increase in distance on anteroposterior chest radiograph between the thoracic spine and the medial border of the scapula, known as the scapular index [161]. Recovery of brachial plexus function after scapulothoracic dissociation is unreliable at best, especially after nerve root avulsion [159,160,162]. Bhattacharyya T, Mehta P, Smith M, et al: Routine use of wound vacuum-assisted closure does not allow coverage delay for open tibia fractures. Johansen K, Daines M, Howey T, et al: Objective criteria accurately predict amputation following lower extremity trauma. Ghaemmaghami V, Sperry J, Gunst M, et al: Effects of early use of external pelvic compression on transfusion requirements and mortality in pelvic fractures. Smith W, Williams A, Agudelo J, et al: Early predictors of mortality in hemodynamically unstable pelvis fractures. Ekholm R, Tidermark J, Tornkvist H, et al: Outcome after closed functional treatment of humeral shaft fractures. Ekholm R, Adami J, Tidermark J, et al: Fractures of the shaft of the humerus: an epidemiological study of 401 fractures. The relationship between tissue pressure, compartment, and the distance from the site of the fracture. Kakar S, Firoozabadi R, McKean J, et al: Diastolic blood pressure in patients with tibia fractures under anaesthesia: implications for the diagnosis of compartment syndrome. Heemskerk J, Kitslaar P: Acute compartment syndrome of the lower leg: retrospective study on prevalence, technique, and outcome of fasciotomies. Fuchs S, Heyse T, Rudofsky G, et al: Continuous passive motion in the prevention of deep-vein thrombosis: a randomized comparison in trauma patients. Patil S, Gandhi J, Curzon I, et al: Incidence of deep-vein thrombosis in patients with fractures of the ankle treated in a plaster cast. Ekholm R, Ponzer S, Tornkvist H, et al: Primary radial nerve palsy in patients with acute humeral shaft fractures. Kenny C: Compartment pressures, limb length changes and the ideal spherical shape: a case report and in vitro study. Lindahl J, Hirvensalo E, Bostman O, et al: Failure of reduction with an external fixator in the management of injuries of the pelvic ring: long- term evaluation of 110 patients. Pohlemann T, Braune C, Gansslen A, et al: Pelvic emergency clamps: anatomic landmarks for a safe primary application. Zannis J, Angobaldo J, Marks M, et al: Comparison of fasciotomy wound closures using traditional dressing changes and the vacuum-assisted closure device. The degree of injury and depth of burn are proportional to the amount of energy delivered to the tissue and duration of exposure to the offending agent. In 2015, approximately 450,000 burn-related injuries were reported in the United States, necessitating approximately 40,000 hospitalizations. All human tissue is susceptible to burn injury, although skin and aerodigestive tissues are commonly involved. Ectodermally derived epidermis is vital for fluid management, pigmentation, and protective immunologic functions, but the epidermis has little structural integrity at seven cells thick. What the epidermis lacks in thickness it makes up for with its regenerative properties; the layer’s abundant stem cells heal isolated injury of this layer without scar. The dermis gives skin its strong mechanical integrity and as such is the focus of much of acute burn care [2]. Accurate burn depth assessment is critical in the patient’s clinical management but remains a qualitative appraisal. Significant “bench to bedside” work has been performed using both laser Doppler and hyperspectral imaging to quantify tissue injury; however, clinical judgment remains the gold standard [3]. Burn depth occurs on a spectrum: superficial burns involve the thin epidermis only; partial-thickness or second-degree burns disrupt the epidermis’ basement membrane and encroach into the dermis, resulting in blisters; the dermis is burned in full-thickness or third-degree burns, which often look pale, ashen, and leathery. Third- and fourth-degree burns typically outstrip the body’s regenerative capacity and require operative excision of damaged tissues and restoration of skin integrity. Because of the body’s inflammatory response to the initial traumatic insult, burn depth may change over time, colloquially described as “deepening. Airway should be evaluated and secured when appropriate to facilitate breathing and ongoing oxygenation, followed by an evaluation of the patient’s circulation. Primary traumatic survey should encompass evidence of head injury, long bone trauma, and acute hemorrhage. Accurate information around the mechanism of burn and location (closed or open space) inform the clinician’s suspicion about concomitant injuries such as inhalational injury, deep muscle injury from electrocution or fractures from a high fall, and the like. Age of the burned patient is of vital importance when predicting a patient’s mortality; with increasing age, risk of death is greater with lower total body burn surface area. The clinical paradigm has shifted in the past 35 years to early surgery (within 5 days), and survival rates of major burns—in conjunction with advances in critical care—have dramatically improved [7]. Because of the interdisciplinary care required to take care of the burned patient, prompt transfer to certified burn centers in accordance with American Burn Association guidelines has been shown to have the best outcomes, especially in cases of inhalational burns [8]. Kinins, serotonin, histamine, prostaglandins, and oxygen radicals are the vasoactive mediators released in response to the burn injury and stimulate systemic vascular permeability. These mediators increases vascular permeability, with resultant decreased capillary oncotic pressure and subsequent severe total body edema, even in nonburned tissues. Albumin is functionally lost into the interstitium, thereby increasing extravascular oncotic pressure, compounding the edema [10]. The burned patient’s fluid “requirement” should be thought of as that volume needed to optimize organ function and tissue perfusion. If the patient’s urine output is greater than 1 mL/kg/h, the infusion rate should be decreased and titrated appropriately. If urine output remains high, urine electrolytes and glucose should be evaluated with specific attention to glycosuria secondary to the burn hypermetabolism. Central venous access may be necessary to deliver the appropriate resuscitation in a timely manner and is ideally, but not essentially, placed through nonburned tissue [12]. The use of pressors requires clinical judgment and should be employed only in settings of persistent hypotension despite adequate fluid resuscitation with both crystalloid and colloid rescue therapy. For patients with persistent oliguria, preexisting renal failure, or congestive heart failure, a pulmonary artery catheter or the equivalent measuring tool to quantify hemodynamics is advised [13].

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Hypoglycemia cheap quetiapine 100mg, low antithrombin cheap quetiapine 100 mg fast delivery, and high ammonia levels can help distinguish fatty liver from other pregnancy complications [59] quetiapine 200mg line. Therapy includes termination of pregnancy or supporting the patient with plasma exchange until the fetus is viable order quetiapine 200mg with amex. The bleeding is caused by a combination of factor depletion, platelet dysfunction, thrombocytopenia, and excessive fibrinolysis. Most often the thrombosis is venous, but arterial thrombosis and nonbacterial thrombotic endocarditis have been reported [65]. Measurement of laboratory tests that will reflect the basic parameters essential for both blood volume and hemostasis is helpful. Replacement therapy is based on the results of these laboratories and the clinical situation of the patient (Table 91. Additional discussion regarding transfusion of blood products in critically ill patients is found in Chapter 116. In this case, the purpura fulminans starts with a painful red area on the lower extremities that rapidly progresses to a black ischemic lesion. Secondary purpura fulminans is most often associated with meningococcemia infections, but it can occur in any patient with overwhelming infection [70]. Post-splenectomy sepsis syndrome patients and those with functional hyposplenism due to chronic liver diseases are also at risk [71]. Patients present with signs of sepsis, and the skin lesions often involve the extremities and may lead to amputation. As opposed to primary purpura fulminans, those with secondary purpura fulminans will have symmetrical ischemic lesions at the distal parts of the body (toes and fingers) that ascend as the process progresses. Adrenal infarction (Waterhouse–Friderichsen syndrome) can occur which leads to severe hypotension [72]. Primary purpura fulminans, especially cases with post-varicella autoimmune protein S deficiency, may respond to plasma infusion titrated to keep the protein S level more than 25% [67]. Critically ill patients with secondary purpura fulminans have been treated with plasma drips, plasmapheresis, and continuous plasma ultrafiltration. Much attention has been given to replacement of natural anticoagulants such as antithrombin as therapy for purpura fulminans, but randomized trials using antithrombin have shown mostly negative results [75]. Many patients need debridement and amputation; in one review, approximately 66% of patient required amputation [76]. The syndrome has occurred in association with the use of advanced-generation cephalosporins (notably cefotetan and ceftriaxone), and it has been reported with carboplatin and oxaliplatin [77]. The clinical syndrome associated with cephalosporin starts 7 to 10 days after receiving the drug and may occur following a single dose given as surgical prophylaxis. The patient may be misdiagnosed as having sepsis and be reexposed to the cephalosporin, resulting in worsening of the clinical picture. Approximately 24 to 96 hours after quinine exposure, the patient becomes acutely ill with nausea and vomiting. Some patients, besides having antiplatelet antibodies, also have antibodies that bind to red cells and neutrophils that may lead to the more severe syndrome. Early recognition of the hemolytic anemia (and the suspicion that it is drug-related) is important for early diagnosis so that the culprit drug can be discontinued. One of the agents most commonly associated with drug-induced thrombocytopenia in the critical care setting is vancomycin. The 9 thrombocytopenia is acute and severe (below <10 × 10 per L), is durably refractory to platelet transfusions, and resolves within days of stopping the drug [80]. In patients with a possible drug-induced thrombocytopenia, the primary therapy is to stop the suspect drug. Patients with severe thrombocytopenia should receive platelet transfusions because of the risk of fatal bleeding [81]. However, with vancomycin-induced thrombocytopenia, the patient may be refractory to platelet transfusion [80]. If there are multiple risk medications, the best approach is to stop any drug that is strongly associated with thrombocytopenia (Table 91. Patients with hemophagocytosis appear to have higher rates of multiple organ system failure and higher mortality rates. Inflammatory cytokines, especially monocyte-colony stimulating factor, are thought responsible for inducing the hemophagocytosis. Three members of the Ehrlichia/anaplasma family have been reported to cause infections in humans [85]. Patients may have central nervous system signs and marked elevation of the serum levels of liver enzymes. In many patients, the buffy coat reveals the organisms bundled in a 2 to 5 µm morula in the cytoplasm of the granulocytes or monocytes. Consideration of ehrlichiosis is important because highly specific therapy is doxycycline, which is a drug not routinely used for therapy of sepsis syndrome. Patients suffer a flu-like prodrome and then rapidly develop a noncardiac pulmonary edema resulting in profound respiratory failure [89]. Marked hemoconcentration is also present because of capillary leak syndrome with the hematocrit reaching in some patients as high as 68%. In the southern United States, dengue is becoming an increasing problem, and fatal cases of arenavirus have been reported in California [93]. A key sign is that patients will experience profuse bleeding from the gastrointestinal tract and mucosal bleeding often out of proportion to the observed coagulation defects. Given the propensity of many of these infections to spread to health care workers, precautions should be taken to prevent nosocomial spread [95]. In the patient who is totally refractory to platelet transfusion, it is important to consider whether a drug has resulted in antiplatelet antibodies (especially vancomycin) [97]. Use of antifibrinolytic agents such as epsilon aminocaproic acid or tranexamic acid may decrease the incidence of minor bleeding but are ineffective for major bleeding [98]. These patients develop renal failure, encephalopathy, adult respiratory distress syndrome (often with pulmonary hemorrhage), cardiac failure, dramatic livedo reticularis, and worsening thrombocytopenia. Many of these patients have preexisting autoimmune disorders and high titer anticardiolipin antibodies. Early recognition of this syndrome can lead to quick therapy and resolution of the multiorgan system failure. Posttransfusion Purpura Patients with this rare disorder develop severe thrombocytopenia (<10 × 9 10 per L), and often severe bleeding, 1 to 2 weeks after receiving blood products [101]. For unknown reasons, exposure to the antigens from the transfusion leads to rapid destruction of the patient’s own platelets. The diagnostic clue is thrombocytopenia in a patient, typically female, who has received a red cell or platelet blood product in the past 7 to 10 days. Treatment consists of intravenous immunoglobulin [102] and plasmapheresis to remove the offending antibody (see Chapter 96). Hach-Wunderle V, Kainer K, Krug B, et al: Heparin-associated thrombosis despite normal platelet counts. Kang M, Alahmadi M, Sawh S, et al: Fondaparinux for the treatment of suspected heparin-induced thrombocytopenia: a propensity score- matched study. Donegani E, Hillebrandt D, Windsor J, et al: Pre-existing cardiovascular conditions and high altitude travel.

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