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The clinical picture is that of death due to morphine- induced respiratory depression purchase 15 mg mobic free shipping gelatin for arthritis in dogs. They observed an effect of the different genotypes on respiratory depression with an increased risk for a reduction in respiratory rate in certain variant gene combinations best purchase mobic arthritis medication that was recalled. These data are best explained by a lesser efficacy of the variant P-glycoprotein to transport fentanyl away from the brain cheap 7.5mg mobic with visa arthritis pain early morning. Opioid-induced Respiratory Depression 1330 Mechanisms of Opioid-induced Respiratory Depression The drive to breathe is generated in multiple respiratory centers in the brainstem buy mobic online now arthritis leg pain. For example, acidosis, hypercapnia, and hypoxia will cause hyperventilation, while hypocapnia and alkalosis will reduce minute ventilation. Furthermore, depression of the93 chemo- and arousal reflexes by opioids will cause a delayed and less forceful 1331 response to upper airway obstruction. Recent data indicate that most90 patients receiving opioids, whether diagnosed with obstructive sleep apnea syndrome or not, develop both central and obstructive apneic events resulting in recurrent hypoxemia during the first three to five nights postoperatively. While supplemental oxygen results in fewer hypoxic events, it has a serious disadvantage as it masks hypoventilation and early detection of an obstructive respiratory event because the lungs are primed with supplemental oxygen. Use of a pulse oximeter, especially in the presence of supplemental oxygen administration, is not a valid measure of the adequacy of ventilation. An example of the inability to detect an apneic event using pulse oximetry while on supplemental oxygen is given in Figure 20-12. A subject received a remifentanil bolus causing rapid respiratory depression and a reduction in respiratory rate, both during air and oxygen breathing. The metrics in the literature defining respiratory depression are inconsistent, the data are predominantly retrospective, and most studies rely on intermittent sampling of data. A recent systematic review of the literature on postoperative opioid- induced respiratory depression estimates an average incidence of 0. This would suggest that only one in 200 patients90 develops a respiratory event from opioids that requires an intervention such as the administration of naloxone. Accidental deaths from opioids in chronic cancer pain patients are often falsely attributed to the progression of the underlying disease. Recently, there has been an alarming increase in deaths from accidental opioid overdose among patients being treated for chronic noncancer pain. Unfortunately, no valid data are available on the incidence of opioid-induced respiratory depression in chronic pain patients on strong opioids. During air breathing the depression in ventilation is apparent from the reduced oxygen saturation (apart from the reduction in ventilation and respiratory rate). During administration of supplemental oxygen the pulse oximeter does not detect the apneic event. High-inspired oxygen concentration further impairs opioid-induced respiratory depression. These include obese patients, patients with (central or peripheral) hypopneic and apneic periods during sleep, patients with neuromuscular disorders, (premature) neonates, chronic opioid users, and elderly patients. One particularly well-88 documented case report of a postoperative lethal opioid-induced respiratory event is given by Lötsch et al. Following surgery she received four intravenous injections of morphine, with a total dose of 35 mg over 2 hours (almost 0. While the patient was comfortable and in no apparent distress directly after the last morphine dose, 40 minutes later the patient had “deep respiratory depression followed by a fatal cardiac arrest. The physicians involved in this case did not take into account the very slow passage of morphine across the blood–brain barrier causing a peak in central effect 1 to 2 hours following peak plasma concentration. And while the onset of analgesia occurred relatively rapidly following the last dose, the fatal respiratory depression occurred 40 minutes later. This is an important observation and implies that patients who show limited analgesic effect in response to opioid treatment are better off with other analgesic options (e. The curves of patients in pain will have a different form, typically more skewed to the left. However, since pain is not a constant in postoperative pain patients or chronic pain patients, the curves shown are still applicable to postoperative patients. Reversal of Opioid-induced Respiratory Depression As noted above, the drug of choice in case of life-threatening respiratory depression or the inability to resume spontaneous breathing is naloxone. Both61 antagonists are nonspecific, meaning that they antagonize all pharmacologic effects of opioids. But the rate of decay of naloxone in plasma is relatively short (t½elim 30 minutes), resulting in “renarcotization” when used to reverse effects from opioids with a longer plasma half-life than naloxone. However, opioid concentrations are often just above the threshold for respiratory depression, and intravenous titration of naloxone 40 to 80 μg bolus doses to cumulative doses of less than 400 μg is often sufficient to restore spontaneous breathing. Respiratory depression from opioids occurs90 at higher receptor occupancy rates than analgesia. Therefore, analgesia is not compromised with careful titration of naloxone to respiratory effect. Large doses of naloxone, as commonly used in resuscitation, will reverse analgesia immediately and may predispose patients to pain and catecholamine- associated hypertension and cardiac ischemia, if not monitored properly. For remifentanil the use of bolus naloxone doses in case of respiratory depression is unnecessary. The termination of the infusion will provide a rapid return of spontaneous breathing. In recent years various drugs have been developed that reverse opioid- induced respiratory depression without affecting analgesia. These drugs stimulate the respiratory system at central (brainstem) and peripheral (carotid body) sites. However, doxapram produces various side effects (anxiety/panic attacks, hypertension, tachycardia, sweating, convulsions). Two drugs A and B have similar analgesic potencies (top), but differ in their potency to induce side effects (middle). The simplified utility is the difference between the probability for analgesia, P(analgesia), and the probability for side effects, P(side effects). The probability of an analgesic effect greater than 50% minus the probability of side effects greater than 50% is given for the two opioids. C: Fentanyl utility functions in individuals with a high and low analgesic response to fentanyl. A high efficacy for analgesia is coupled to a low probability for respiratory depression and vice versa. On the ward “spot” oxygen saturation measurements by regular nurse visits are insufficient to detect or predict the occurrence of life-threatening respiratory events. A recent study in 833 patients recovering from noncardiac surgery in which continuous oxygen saturation was measured up to 48 hours after surgery showed that hypoxia was common and prolonged. The saturation values recorded in medical records seriously underestimated the presence, duration, and severity of postoperative hypoxemia (21% of patients had oxygen saturation levels <90% for 10 minutes or more per hour; 8% had saturation levels <85% for 5 minutes or more per hour, Fig. Arousal is a “wake-up” from a state of sleep or sedation, and allows the patient to open his or her throat and hyperventilate to overcome the preceding period of hypoxemia. Postoperative respiratory events are often episodic, with arousals and hyperventilation in- between events. This will cause repetitive triggering of the oxygen saturation monitoring alarm and possibly alarm fatigue of the nursing staff.
Females have variable enzyme levels and therefore exhibit a wide range of severity generic 7.5mg mobic mastercard arthritis in dogs injections. This image shows numerous lipid vacuoles (arrow) with a proteinaceous matrix ﬁlling a distended capil- lary loop buy mobic discount what good for arthritis in the knee. The glomeruli in Fabry’s disease show cytoplasmic vacuolization generic 15 mg mobic mastercard arthritis in both ring fingers, most prominent in podocytes purchase mobic 7.5mg rheumatoid arthritis diet book, as shown here. Admixed with the lipid is granular electron-dense proteinaceous material of unknown composi- tion. In this glomerulus from a female carrier of glomerulus show striking enlargement and vacuolization. The mesan- Fabry’s disease, who presented with proteinuria and normal serum cre- gium shows no abnormality. Masson trichrome stain atinine, silver stain reveals two vacuolated podocytes, one of which is markedly enlarged. This glomerulus is from a female carrier of embedded tissue for electron microscopy allows appreciation of the Fabry’s disease presenting with proteinuria and normal serum creati- true extent of lipid deposition. This electron micrograph shows numerous osmophilic (black) lamellated lipid inclusions within the podocytes. In nephrosialidosis, the oligosaccharide storage products accumulate within glomerular podocytes and endothe- lial, interstitial, and occasionally proximal tubular cells. This electron microscopic image shows the distinctive lamellated nature of the intracellular inclusions, which are known as myelinosomes or myeloid bodies 254 6 Glomerular Diseases Fig. Hale’s colloidal iron stain graphically demonstrates the magnitude of the oligosaccharide storage (Courtesy of Fig. Remaining are largely empty intracellular vacuoles containing a small quantity of residual electron-dense membranous material. They have coarse facial features, psychomotor retardation, joint contractures, deformed long bones, valvu- lar abnormalities, respiratory symptoms, and renal disease. Proximal tubular dysfunction occurs with hypercalciuria, hyperphosphaturia, and aminoaciduria. There is more abundant lamellar electron- dense material in the podocytes than in the above case. The disease ﬁndings bear strong resem- blance to those observed in nephrosialidosis, but interstitial cells and endothelial cells are not affected. The vacuoles have modest amounts of lamel- lar material, which might raise the possibility of Fabry’s disease. Renal enlargement, proteinuria, and distal tubular aci- dosis develop, followed by nephrocalcinosis and renal failure. Histologically, glomerulomegaly is present and tubules are vacuolated as a result of extraction of the retained glycogen. The vacuolated or cleared-out apical cytoplasm (arrow) is more apparent at higher magniﬁcation. The mutations result in lysosomal accumulation of cystine lead- ing to multiorgan damage. Patients present with Fanconi syndrome, which if untreated is followed by renal failure and death by age 10 years (see Figs. Juvenile cystinosis causes mild mesan- gial matrix expansion and affects the podocyte in a distinctive fashion, causing multinucleation. There were scattered multinucleated podo- cytes in this case, although not every glomerulus showed this ﬁnding. The transsphenoidal approach is the result of an evolution- ary process rather than a revolutionary one. Many neurosurgical (and nonneurosur- gical) pioneers have contributed to their development. The evolution of transsphenoidal surgery is a complex tale of in- novative leaps in ideology coupled with periods of exten- sive surgical experimentation interspersed with a period of complete rejection of the technique. I Ancient Egyptians The ancient Egyptians were one of the frst groups to care- fully study and document the anatomy of the human body and undoubtedly were the frst to reach the brain through the transnasal route. Head and skull base features of nine Egyptian mum- facial transsphenoidal exposure. Although his frst opera- Theodor Kocher (Cushing’s mentor) modifed Schlofer’s tion was unsuccessful, in 1906 he reported on 10 patients approach by submucosal removal of the septum, allowing treated with craniotomy. However, it was Oskar Hirsch, a rhi- to resect a pituitary tumor using the subtemporal approach nologist, who developed a completely endonasal transsep- of Horsley in a patient with acromegaly but were unsuccess- tal transsphenoidal operation in 1910, based on his mentor ful. Kiliani developed ing later improved the technique, using Kocher’s submucosal an intradural bifrontal approach in cadavers in 1904, hoping resection of the septum and a nasal speculum (a modifed that it would lead to improvement of the technique. This approach was popular both before and after the emergence of transsphenoidal operations. Diagram demonstrating the lateral rhinotomy exposure of the septum and nasal turbinates of the nose just prior to exposure of the sphenoid sinus described by Schlofer. At the same time, in the United States, Albert Halstead of Chicago modifed the curvilinear incision through the na- solabial junction suggested by Allen Kanavel. He performed his frst transsphenoidal operation in 1909 for a patient with acromegaly. From 1910 to 1925, Cushing operated on 231 pituitary tumors us- ing the sublabial transsphenoidal approach, with a mortality Fig. Meanwhile, Norman Dott, who learned the transsphenoi- dal approach in 1923 from Cushing during a traveling fellow- ship at the Peter Bent Brigham Hospital in Boston, returned to Edinburgh, where he continued to advocate this proce- dure. Another key factor in the preservation of the transsphe- noidal approach was the contribution of Hirsch and Hamlin. Oskar Hirsch immigrated to the United States after being expelled from Austria by the Nazis in 1938. Hirsch and Hamlin extolled the virtues of the transsphe- noidal approach and reported excellent long-term results. I Revival of the Transsphenoidal Approach Numerous innovations introduced in the 1950s played an im- portant role in the resurgence of interest in transsphenoidal surgery. With the introduction of cortisone and antibiotic therapy, total hypophysectomy could be performed with sig- nifcantly reduced mortality and better long-term success. Note the anesthetic tube in the Guiot visited Dott, observed his meticulous technique and special mouth gag designed by Cushing. This allowed him to apply the transsphe- Cushing’s intense interest in intracranial surgery led him to noidal approach to craniopharyngiomas, clivus chordomas, pursue and develop transcranial approaches to the pituitary and parasellar lesions, and thus he played a pivotal role in gland. As he developed expertise and confdence in these the resurrection of the transsphenoidal approach during the approaches, he reduced his mortality rate with the transcra- following two decades. As a trainee under Guiot in Paris, Hardy of Montreal treated many patients with suprasellar tumors, especially continued the use of televised radiofuoroscopic control,17 meningiomas and craniopharyngiomas, by a transfrontal which gave him the opportunity to perform more exten- approach, which enabled him to verify suprasellar tumors sive resections of large midline suprasellar tumors.
Postoperative pain is usually minimal and responds well to nonopiate and opiate medications buy mobic with mastercard rheumatoid arthritis pathology. Laser techniques have advantages over traditional electrocautery approaches buy generic mobic on line arthritis pain neck symptoms, particularly related to traditional irrigation fluid restrictions buy mobic 15mg fast delivery arthritis medication pregnancy. Furthermore buy mobic 15mg otc arthritis relief for lower back, the potential for systemic absorption may be reduced owing to the lower irrigation infusion rates and pressures necessary for laser procedures. Irrigating Solutions and Transurethral Resection Syndrome Key to a surgeon’s endoscopic view during transurethral procedures is a visually clear irrigating solution, infused with a pump or via gravity (and drained away) to flush out blood and resected tissue and keep space between structures. The crystalloids have current- dispersing properties owing to their ionic characteristics that make them unsuitable for use with unipolar electrocautery. When absorbed in significant amounts, nonelectrolytic irrigation solutions combine electrolyte disturbances with hypervolemia. Notably, newer transurethral bipolar electrocautery and laser techniques now allow irrigation with isotonic crystalloid solutions (e. Of available irrigating solutions, distilled water is rarely utilized owing to its hypotonicity. Water intoxication with distilled water rapidly causes severe hyponatremia leading to hemolysis, hemoglobinemia, and renal failure. Glycine, an amino acid normally metabolized to ammonia, may cause a depressed mental status and even coma (due to hyperammonemia) that can last 24 to 48 hours postoperatively. In the awake patient with a regional block, a classic triad of symptoms has been described that consists of an increase in both systolic and diastolic pressures associated with an increase in pulse pressure, bradycardia, and mental status changes. First, the surgeon should be informed of the patient’s status change so that the procedure can be completed or terminated as quickly as possible. Symptomatic patients with serum sodium concentrations less than 120 mEq/L should have their extracellular tonicity corrected with hypertonic saline. Sodium chloride in a 3% solution should be infused at a rate no greater than 100 mL/hr. Serum electrolytes should be followed closely and the hypertonic saline discontinued when the patient is asymptomatic or serum sodium concentration exceeds 120 mEq/L. Treatment with hypertonic saline has been associated with development of demyelinating central nervous system lesions (central pontine myelinolysis) owing to rapid increases in plasma osmolality, and this approach should be reserved for patients with severe, life-threatening symptoms. Up to 50% of patients with an initial stone episode will have a recurrence within 5 years. Stones form when the concentration of stone-forming salts in the urine is elevated (e. This results in supersaturation of the urine with salts, allowing crystals to form and grow, particularly in situations where urine volume is low. This pathophysiology explains the principles of the medical management of kidney stones: increasing urine volume and maneuvers to restore urinary salt balance through dietary and medical treatment. Ultrasound imaging is also informative for stones in the kidney and proximal ureter but cannot show the distal ureter and may miss smaller stones. Intravenous pyelography is rarely used because it offers no added information compared to other diagnostic modalities and exposes the patient to radiation and contrast-related renal injury. The so-called medical expulsive therapy to promote ureter relaxation and the spontaneous passage of small ureteral stones involves treatment with calcium channel blockers (e. If stones do not pass spontaneously or respond to medical expulsive therapy, various surgical options can be considered, as discussed earlier (Fig. Typical calcium salt stone disease presents in the third to fifth decades of life237 and is commonly associated with comorbidities such as obesity, hypertension, and hyperparathyroidism. Bladder stones are often diagnosed in patients with poor voiding capacity, for example, paraplegic patients, and the associated perioperative concerns for these patients should be addressed. Although paraplegic patients with sensory deficits below T6 lack pain perception for cystoscopy procedures, they are at risk for autonomic hyperreflexia and require anesthesia to block the afferent stimulation that can provoke this reaction (e. This can be achieved with deeper levels of general anesthesia or regional anesthesia. Patients with recurrent nephrolithiasis may be receiving chronic opioid therapy and demonstrate tolerance intra- and postoperatively. In contrast, when severe colic is alleviated by surgery for an opioid-naive patient already treated with opiates, postoperative somnolence is quite common. Renal colic is often associated with nausea and vomiting, and preoperative aspiration prophylaxis should be considered. Unless open surgery is planned, there is rarely a need for blood transfusion for stone surgery. Selection of appropriate monitors should be dictated by patient comorbidities, because significant blood loss or fluid shifts are unusual with these procedures. However, if difficulty achieving vascular access during a procedure is anticipated (e. Antibiotic prophylaxis is important, particularly with infected stones or pyelonephritis. When lasers are required, appropriate eye protection should be provided for the perioperative team and patient. Intraoperative Considerations Compared with other more invasive urologic procedures, stone surgeries generally do not involve large amounts of blood loss or fluid shifts, with the possible exception of percutaneous nephrolithotripsy (see later). Information about anesthetic choice and potential intraoperative issues is discussed in the 3580 individual sections and in the sections on nephrectomy and transurethral surgery elsewhere in this chapter. Monitoring decisions and anesthetic choices should be made on the basis of patient comorbidity, and intraoperative care should focus on those as well. Postoperative Considerations Postoperative concerns for urolithiasis procedures are generally minor. Interestingly, patients with severe renal colic prior to less invasive surgeries (e. However, immediately following urinary tract instrumentation, many patients experience rather uncomfortable bladder and ureteral spasms. Occasionally, open surgery is required for upper urinary tract stone removal, with postoperative concerns comparable to those for nephrectomy patients having similar incisions; these include pain, which may be sufficient to require epidural analgesia, and monitoring requirements to ensure that adequate resuscitation related to any blood loss has occurred. Monitoring the adequacy of urine output and maintaining any urinary irrigation or drainage system (e. After extraction or lithotripsy of stones, particularly struvite stones or in the setting of pyelonephritis, patients may develop a pattern of rigors, hypotension, and fever, which can lead to shock. Urine culture results can be misleading in predicting which patients will develop sepsis because urine below the level of a stone may be clean, yet urine upstream of the stony obstruction may be infected. A sepsis picture can be noted during the procedure but is more likely to occur postoperatively. Indications of intravascular bacterial seeding from infected urine needs prompt attention with blood cultures, fluids and resuscitation, and institution of appropriate antibiotic therapy to prevent more serious sequelae of a sepsis syndrome. This requires transmission of the sound wave beam via an interface with the patient’s body. In addition to the significant positioning maneuvers associated with this procedure, patients are prone to hypothermia during the procedure.
Greater levels of hypotension and elevated triglyceride levels were observed with the use of propofol order generic mobic line rheumatoid arthritis blood test. Like dexmedetomidine purchase mobic 15 mg without prescription juvenile arthritis in the knee, opiates do not reliably produce amnesia 7.5mg mobic amex arthritis relief in neck, and are not appropriate as single agents in patients who require paralysis cheap mobic 7.5 mg visa arthritis treatment machine. Morphine should be avoided in patients with renal failure due to active metabolites that accumulate in the presence of impaired 4128 renal function. A single trial has demonstrated a benefit in mortality and ventilator-free days, but routine use is discouraged until these results are validated. Delirium and Neurocognitive Complications Neurocognitive complications including delirium and prolonged cognitive dysfunction are associated with a number of sedative medications, and may be more common in patients treated with deeper levels of sedation. The distinguishing characteristics of delirium include an acute onset and fluctuating course, inattention, disorganized thinking, and altered level of consciousness. Although some literature supports the notion that benzodiazepine use may be associated with an increased frequency of delirium, two well-conducted trials failed to show a reduction in delirium in patients randomized to dexmedetomidine compared to benzodiazepine. The 4129 only randomized, controlled trial of such use did show a reduction in periods of delirium with regular quetiapine administration, but the study was small. A systematic review of a number of pharmacologic prevention or treatment strategies (e. Approximately one-third will have signs and symptoms of cognitive dysfunction 12 months after discharge. Further, long-term follow-up of patients enrolled in sedation trials has not found sedation regimens promoting light sedation or daily awakening to be associated with increased long-term cognitive, psychological, or functional problems. At some level, nosocomial infections are unavoidable and occur because of the nature of intensive care—patients are critically ill with altered host defenses, they require invasive devices (endotracheal tubes, intravascular catheters, etc. On the other hand, many nosocomial infections are preventable with relatively simple interventions. Sinusitis Radiographic sinusitis is common in critically ill patients with indwelling oral and nasal tubes. Nasotracheal intubation confers a greater risk than does orotracheal intubation of radiographic sinusitis, occurring in approximately 95% and 25% of patients with nasal and oral tubes after 1 week of intubation, respectively. Prevention of sinusitis should focus on efforts to improve sinus drainage, including semirecumbent positioning and avoidance of nasal tubes. If radiographic sinusitis is documented, any nasal tubes should be removed, and nasal irrigation and short-term administration of nasal decongestants should be considered. If the patient is severely ill, broad-spectrum antibiotic coverage should be considered. If these maneuvers do not result in resolution of signs and symptoms of sinusitis in 2 to 3 days, otolaryngologic consultation and consideration of sinus drainage procedures may be undertaken. In general, early-onset organisms are associated with zero or low attributable mortality, whereas late-onset organisms, particularly Pseudomonas and Acinetobacter species, are associated with higher mortality. The simplest and least expensive interventions are strict handwashing between patients, and semirecumbent 4132 positioning of the patient (head-of-bed angle at 30 degrees or greater from horizontal). The use of acid suppression therapy to prevent gastrointestinal bleeding is more controversial. Thus, gastrointestinal acid suppression therapy may be reserved for high-risk patients, and sucralfate may be considered as an alternative agent to acid-suppressive regimens despite its potentially reduced effectiveness. Invasive strategies typically involve collection of either tracheal aspirate specimens or bronchial–alveolar specimens using lavage or protected brushes, and then quantitating bacterial growth in the laboratory. Antibiotics can then be narrowed in spectrum or discontinued altogether depending on the results from quantitative cultures after 48 to 72 hours (Table 57-6). This approach is known as “de-escalating therapy” and is designed to ensure adequate antibiotic treatment up front, but avoid overuse of antibiotics in the long term. It is unclear whether intermediate courses of therapy would have avoided infection recurrence. However, the incidence of bacteremia is affected by several factors, including the conditions and technique of insertion, type and location of catheter, and the duration of catheterization, and can vary widely from study to study. This includes pre-insertion handwashing, full gown and gloves, and the use of a large barrier drape. In addition, skin cleansing with22 chlorhexidine is more effective than other agents at reducing catheter-related infection. However, routine catheter replacement at 3 or 7 days does not reduce the incidence of infection, and results in increased mechanical complications. Catheters coated with either antiseptics (chlorhexidine and silver sulfadiazine) or antibiotics (rifampin and minocycline) reduce bacterial colonization of catheters as well as bacteremia. Routine flushing of catheter ports with heparin reduces both the incidence of thrombosis and infection. However, heparin solutions contain antimicrobial preservatives and it is unclear if the heparin or the preservative is responsible for the beneficial effect. Depending on the patient’s severity of illness, a strong suspicion of catheter-related bacteremia should trigger the institution of broad-spectrum antibiotic coverage, including coverage for methicillin-resistant staphylococcal species and nonlactose–fermenting gram- negative rods, until culture results return, with subsequent de-escalation of therapy. Positive cultures from sterile fluid remain the gold standard, but may take 72 to 96 hours to turn positive and may be positive in only 50% of autopsy-confirmed infections. Candida is frequently cultured from the urine and sputum, but treatment is usually not necessary, as Candida pneumonia is unlikely and candiduria often clears without treatment, mostly with discontinuation of the bladder catheter. In addition, candiduria often recurs after initially successful antifungal therapy. True Candida peritonitis is also difficult to separate from contamination of culture specimens, but given that the mortality associated with Candida peritonitis is approximately 50%, treatment is warranted if clinical signs suggest infection. Disseminated blood-borne Candida infection can result in endophthalmitis, endocarditis, and hepatic and pulmonary abscesses. It is likely to occur when initial treatment of candidemia is delayed, and is associated with a high mortality. Prophylactic therapy with fluconazole may be effective at reducing the risk of invasive Candida infection in high-risk patients, but this strategy has not been associated with improved mortality in the nonneutropenic population, and may increase the incidence of invasive infection with more resistant species, such as C. However, care should be taken to de-escalate therapy after several days in the absence of positive cultures or clinical response. Documented Candida bloodstream infection should be treated aggressively, with therapy started promptly and continued for at least 2 weeks after the last positive blood culture. An ophthalmologic examination is warranted in patients with documented or suspected bloodstream infection, as patients with endophthalmitis may require longer courses of therapy. Intravascular catheters that are potential sources of bloodstream infection should be removed. Treatment of Candida infections has evolved over time, and current guidelines now recommend echinocandins such as caspofungin, micafungin, and anidulifungin as the first-line treatment in most settings. Secondary risk factors among mechanically ventilated patients include renal failure, thermal injury, and possibly head injury, although the latter two factors have not been recently evaluated.