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Although the role70 of colloid in resuscitation of brain-injured patients remains unclear 120mg starlix for sale, it is appropriate to avoid large volumes of hypo-oncotic fluids such as lactated Ringer solution purchase 120mg starlix amex. Hypertonic purchase starlix with amex, hypernatremic solutions, with or without added colloid, appear to fulfill some of these criteria (Table 16-12). Hypertonic solutions exert favorable effects on cerebral hemodynamics, in part because of the reciprocal relationship between plasma osmolality and brain water. Central78 pontine myelinolysis, which follows rapid correction of severe, chronic hyponatremia, has not been observed in clinical trials of hypertonic resuscitation. Despite theoretical considerations favoring the use of hypertonic saline in resuscitation of patients with traumatic brain injury, a subsequent randomized trial failed to demonstrate an improvement in outcome. Pending further preclinical work, the theoretical advantages of such fluids appear most attractive in the acute resuscitation of hypovolemic patients who have decreased intracranial compliance. Although this goal is conventionally accomplished with mannitol, some clinicians prefer hypertonic 1027 saline solutions. However, infusion of hypertonic saline increases intravascular volume, while diuresis secondary to mannitol decreases intravascular volume. Table 16-12 Hypertonic Resuscitation Fluids: Advantages and Disadvantages Fluid Status: Assessment and Monitoring For most surgical patients, conventional clinical assessment of the adequacy of intravascular volume is appropriate. Assessment of hypovolemia is mainly based in physical signs that include oliguria, supine hypotension, and a positive tilt test. In general, oliguria implies hypovolemia, keeping in mind that hypovolemic patients can have adequate urinary output and that urinary output can be misleadingly high. Supine hypotension suggests a blood volume deficit greater than 30%, although in elderly or chronic hypertensive patients, an arterial blood pressure within the normal range could represent relative hypotension. A positive tilt test, defined as an increase in heart rate of at least 20 beats per minute and a decrease in systolic blood pressure of 20 mmHg or more when the subject assumes the upright position, can be falsely negative. In contrast, orthostasis may occur in 20% to 30% of elderly patients despite normal blood volume. In volunteers, withdrawal of 500 mL of blood was84 associated with a greater increase in heart rate on standing than before blood withdrawal, but with no significant difference in the response of blood pressure or cardiac index. In acute hemorrhage, hematocrit decreases slowly as fluid shifts from the interstitial to the intravascular space and more rapidly during administration of fluids. The sensitivities and specificities of measurements of blood and urinary variables to hypovolemia are poor. In prerenal oliguria, enhanced sodium reabsorption should reduce urinary [Na ] to 20 mEq/L or+ less and enhanced water reabsorption should increase urinary concentration (i. Intraoperative Clinical Assessment Both surgeons and anesthesiologists tend to underestimate blood loss, based on assessment of blood on surgical gauze pads, pooled on the floor, and accumulated in the surgical field and suction containers. Assessment of the adequacy of intraoperative fluid resuscitation integrates multiple clinical variables, including heart rate, blood pressure, urinary output, arterial oxygenation, and pH. In patients receiving potent inhalational agents, maintenance of blood pressure within the normal range implies adequate intravascular volume. When measured, a central venous pressure of 6 to 12 mmHg suggests adequate blood volume. Tachycardia is an insensitive and 1029 nonspecific indicator of hypovolemia that is also altered by anesthetic drugs. In severe hypovolemia, the accuracy of indirect measurements of blood pressure diminishes. Under those circumstances, direct arterial pressure measurements are more accurate than indirect techniques. Therefore, in the absence of glycosuria or diuretic administration, a urinary output of 0. Mixed venous hemoglobin desaturation, a specific indicator of poor systemic perfusion, reflects average perfusion in multiple organs and cannot supplant regional monitors such as urinary output. Assessing physiologic responses to fluid87 administration can indicate the adequacy of cardiac preload and facilitate management of hemodynamics. Assessment increasingly depends on dynamic physiologic variables rather than static variables such as central venous pressure. Esophageal Doppler assessment of blood flow in the descending aorta is another promising technique in measuring adequacy of cardiac preload during high-risk surgical procedures. Using the esophageal Doppler to guide administration of colloid boluses, Venn et al. Of note, Horowitz and Kumar speculated that the infusion of95 colloid rather than the monitor-driven algorithm was responsible for the improved results. Large multicenter trials are needed in order to ascertain the benefits of the described novel techniques in perioperative outcomes of patients undergoing high-risk surgery. However, there is96 no apparent benefit for patients other than surgical patients and patients undergoing initial resuscitation from septic shock in the emergency department. Postoperative cardiovascular complications occurred significantly more frequently in the group receiving fluids alone (13/25, 52%, vs. Another specific risk associated with use of fluids to achieve goal-oriented resuscitation is an increased incidence of abdominal compartment syndrome in trauma patients. Disorders of sodium concentration, that is, hyponatremia and hypernatremia, usually result from relative excesses or deficits, respectively, of water. Regulation of total body sodium and [Na ] is accomplished primarily by the+ endocrine and renal systems (Table 16-13). Therefore,+ primary hyperaldosteronism is associated with hypervolemia and with hypertension, but not with abnormal [Na ]. The most common clinical scenarios associated with hyponatremia include the postoperative state, acute intracranial disease, malignant disease, medications, and acute pulmonary disease. Recently, hyponatremia, as well as hypokalemia and hypophosphatemia, have been recognized as complications of immunologic treatment of cancers such as hepatocellular carcinoma and melanoma. Symptoms that can accompany+ severe hyponatremia ([Na ] < 120 mEq/L) include loss of appetite, nausea,+ vomiting, cramps, weakness, altered level of consciousness, coma, and seizures. Because the blood–brain barrier is poorly permeable to sodium but freely permeable to water, a rapid decrease in plasma [Na ]+ promptly increases both extracellular and intracellular brain water. Because the brain does not rapidly compensate for changes in osmolality,106 acute hyponatremia produces more severe symptoms than chronic hyponatremia. The symptoms of chronic hyponatremia probably relate to depletion of brain electrolytes. Once brain volume has compensated for hyponatremia, rapid increases in [Na ] may lead to abrupt brain dehydration. Hyponatremia with a normal or high serum osmolality results from the presence of a nonsodium solute, such as glucose or mannitol, which holds water within the extracellular space and results in dilutional hyponatremia. The presence of a nonsodium solute may be inferred if measured osmolality exceeds calculated osmolality by over 10 mOsm/kg. Hyposmolality is more important in generating symptoms than is hyponatremia per se. In contrast, as glycine or sorbitol is metabolized, hyposmolality will gradually develop, and cerebral edema may appear as a late complication.

Low fow status with a slow decrease for pump exchange or for thrombectomy 120 mg starlix with mastercard, in case of of fow is typical of post-pump thrombosis where unsuccessful washout maneuver starlix 120mg discount. Te log fle of a successful backwash maneuver Te last step of the washout maneuver is is shown in order starlix visa. No neurologic complication has been the fow and power consumption of the pump can recorded with this strategy, as far as reported in be clearly identifed. In a small percentage of patients, the rial blood pressure will show: frst, low blood fow thrombus cannot be found afer the procedure and full lef ventricular ejection at the time of pre- (neither in the Sentinel device nor in the periph- pump obstruction, then retrograde fow indicated eral arteries). Pump Exchange A “lateral implantation” to the descending Pump exchange is the defnitive treatment for aorta can be also performed and represents a suit- intra-pump thrombosis. However, it represents a able solution for patients with a history of com- major cardiac operation, which is performed in plex cardiac operations, where a redo-sternotomy an acute setting on a compromised and hemo- would bear a signifcant risk of damage to the dynamically instable patient. Some clinical signs, for exam- brane oxygenation can be considered for mechan- ple, hemoglobinuria with dark urine, may suggest ical circulatory support during pump exchange, as that severe hemolysis has occurred as a conse- it is a closed circuit, not exposed to air, and allows quence of intra-pump thrombosis and should a lower degree of heparinization compared to the trigger the decision for pump exchange instead traditional heart-lung machine. Indeed, several surgical approaches to pump exchange have been described, each presenting unique advantages and disadvantages [19]. Intensifcation alternative strategy is tirofban (Aggrastat, Merck of anticoagulation is recommended in the & Co. Use of direct thrombin inhibi- tor is described in this context, but is theoreti- 48. Conservative therapy has thrombosis which lowered the percentage of suc- high recurrence rate of thrombosis, because by cess to 21% [22]. However, serious adverse events measuring only indirect parameters it is hard were observed in the treated cases [23]: stroke from to determine whether the thrombus was fully 10% to 15%, bleeding complications at 65%, and resolved or just reduced. No standardized protocol exists; therefore, dosage and time of administration may greatly 48. Furthermore, high option because the rate of bleeding is low, it is dosages of drug are commonly infused (up to safer than thrombolysis, and does not preclude 100 mg) [12], as it is administered systemically. Te key for No consensus exists however, concerning the success is the timing of treatment compared to the administration route of thrombolytic agents and onset of pump thrombosis. Small tricle through a pigtail catheter (rate of 1 mg/min case series reported successful use of eptifbatide for a total dose ranging from 30 to 50 mg) [26], via (Merck & Co. Cardiac transplantation may be a strategy for some patients, but this therapy is limited by donor availability. Awareness of the efect of pump throm- Tere are three main reasons for blood fow bosis on patient outcomes prompted the United obstruction in the outfow graf: kinking of the graf, Network of Organ Sharing in 2013 to allow emer- stenosis of the aortic anastomosis by ingrowth of an gency priority listing for patients with impending intimal fap, or graf thrombosis. No bailout strategy Regular follow-up with transthoracic echocar- is available for destination therapy patients. Fluoroscopy, with intubation of the malfunction due to pump thrombosis, from outfow graf and contrast medium, should be recognition and diagnosis to treatment. Many regarded as the gold standard in assessing stenosis centers worldwide faced pump thrombosis and of the aortic anastomosis. Te ments of the pressure gradient along the outfow device industry focused on this type of adverse graf further support the diagnosis and may be the event in developing new devices. Kinking of the outfow tract time, efort by clinicians should be placed on can be treated by stenting alone and thrombosis novel management strategies since outpatient of the outfow tract by stenting with a covered care is crucial in this topic and every opportu- stent while using cerebral endovascular protec- nity of telemonitoring is welcomed to start the tion [32, 33]. Hubbert L, Sundbom P, Loebe M, Peterzen B, Granfeldt scheduled for pump explantation. However, they H, Ahn H (2014) Acoustic analysis of a mechanical cir- represent a minority of cases. J Am Coll Cardiol 67(23):2758– M, Latif F et al (2012) Development of a novel echocar- 2768. Krabatsch T, Drews T, Potapov E, Weng Y, Pasic M, Hetzer nosis of device thrombosis in continuous-fow left R (2014) Diferent surgical strategies for implantation ventricular assist devices: the Columbia ramp study. Kaufmann F, Hormandinger C, Stepanenko A, and management of pump thrombus in the Kretzschmar A, Soltani S, Krabatsch T et al (2014) HeartWare left ventricular assist device system. A Acoustic spectral analysis for determining pump throm- novel approach using log-fle analysis. J Heart Lung Transplant 34:1535–1541 Registry for Mechanically Assisted Circulatory Support 24. J Heart Lung tinuous-fow right ventricular assist device--repeated Transplant 33:12–22 thrombolysis with two diferent protocols. J Heart Lung Transplant with ventricular assist device thrombosis: an attempt 33:23–34 to avoid reoperation. Soltani S, Kaufmann F et al (2015) Design changes in 192–196 continuous-fow left ventricular assist devices and life 26. Artif novel echocardiograph ramp test for speed optimiza- Organs 39:526–529 tion and diagnosis of device thrombosis in continuous- 27. Analysis of 9 events and pression during speed optimization ramps in patients results after endoventricular thrombolysis. Int J Cardiol supported by continuous-fow left ventricular assist 178:159–161 device: device-specifc performance characteristics 28. J Card Fail tricular assist device outfow cannula obstruction 21(10):785–791 treated with percutaneous endovascular stenting. Grinstein J, Kruse E et al (2016) Screening for outfow Heart Fail 8(1):229–230 cannula malfunction of left ventricular assist devices 29. EuroIntervention 8:43–50 patient with left ventricular assist device outfow graft 33. Eur Heart J 36:2070–2207 48 513 49 Infectious Complications Ezin Deniz, Christina Feldmann, Jan D. Te term “outfow cannula” refers to that sively and difficult to treat due to the presence part of the device connecting the pump device to of biofilms on prosthetic surfaces that markedly the patient’s cardiovascular system. Suture lines reduce the likelihood of successful treatment refer to the surgical anastomoses between pump with anti-infectives alone. Te retrieval of a pathogen teams may be able to aspirate diagnostic fuid sur- or an indistinguishable organism from more than rounding devices by imaging guidance. Objectively Te term “pocket” in these defnitions is used they lie between existing standards for tunneled to describe infections that occur in the body space central lines and implantable intraports [5, 9, or pocket that holds the pump inside the body of 11]. Classically the pocket may be newly fully comprehensive defnitions and defni- created within the abdominal wall or within prox- tions that are practical and useful for clinicians. All percutaneous drivelines may refect the presence of a deeper infection of should be surgically examined at time of removal the pocket space or pump and/or cannula. Patients ofen present with non-specifc aneurysms may be visceral or intracerebral (usu- symptoms such as lethargy, fatigue, fever, or ally presenting as an intracranial hemorrhage). Routine surveillance cultures of exit b sites may be considered as colonization ofen pre- Clostridium difcile infection cedes infection and can serve as valuable infor- Urinary tract infectiona mation for subsequent infection. Cardiothoracic surgeons, diagnosis and ultrasound have become the frst- cardiologists, and, in specialized centers, interven- line study for infections such as cholecystitis [10]. Finally with specifc protocols may have a role in charac- at least two samples of tissue from the pocket area terization of infection but in the surgically “dam- and insertion site of the cannulas into the heart aged” sternum may have limited value [15]. Photograph: Thoratec corporation 1 2 3 49 Possible Probable Proven Defnition No surgical/histology or No surgical/histology Surgical/histology criteria ± purulent discharge ± other criteria with purulent other criteria criteria discharge ± other criteria Surgical or Surgical debridement not Surgical debridement not Involvement of tissues histopathological performed performed superfcial to fascia or No histopathology No histopathology muscle layer = superfcial infection Involvement of tissues deep to fascia or muscle layer = deep infection. All patients should be screened in a similar and coccidioidal infection, respectively.

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It is also necessary to perform preparatory work the day before perfusion buy discount starlix 120 mg, and a little more on the day of perfusion buy generic starlix on line, prior to placenta collec- tion order starlix 120mg overnight delivery, inspection, cannulation, and establishment of homeostasis before experimentation. There are key quality control measures, which must be adhered to in the maintenance of tissue structural integrity and in preventing leakage artifact from the fetal to the maternal circulation. Fetomaternal leakage takes two forms: post- partum breakages in the villous tree structure, which provides a route of least resistance for fetal perfusate escape, along a hydro- static pressure gradient and into the intervillous space, and the bulk fow of perfusate through existing paracellular routes when this fetomaternal hydrostatic pressure differential exceeds approxi- mately 30 mmHg [12, 39, 40]. The latter phenomenon is associ- ated with elevated fetal-side infow hydrostatic pressure, which is evoked by prolonged postpartum ischemia, whereby hemostasis leads to platelet activation and irreversible vasoconstriction within the placental microcirculation. Establishing fetal-side perfusion within 30 min, or at least ensuring a fetal-side fush with heparin- ized perfusate in this time period, would normally ensure a basally relaxed fetoplacental microcirculation, preventing fetomaternal leakage to an acceptable level. Fetal-side (and sometimes maternal-side) infow hydrostatic pressure is monitored in real time, to visualize the ease of postisch- emic blood elution within the frst phase of fetal-side perfusion. A steady-state low fetomaternal hydrostatic pressure differential (below 30 mmHg) is preventative of a perfusate fetomaternal “bulk fow” effect and the loss of barrier architectural integrity, whereas a sustained excessive fetal vascular resistance will compro- mise the tissue structural integrity, by vacuolating the vasculosyn- cytial membrane, leading to an increased diffusional pathway length. According to Fick’s law of diffusion, this would otherwise interfere with nutrient transfer effcacy and the accuracy of inter- pretation and in vivo of pharmacokinetics. Fetal-side infow hydro- static pressure is also directly used in experiments designed to assess the regulation of fetoplacental vascular tone, important in the adequacy of provision of fetal blood fow to and from the pla- centa, in the supply of nutrients and oxygen, and in the elimination of waste products of metabolism. Herein, we discuss the methods for ex vivo dual placental perfusion system and uses of this technique to evaluate (1) vascular function, (2) transplacental clearance, (3) hemodynamic and oxy- genation changes associated with pregnancy complications on 176 Paul Brownbill et al. Circulating water bath, set to deliver heated water to the benchtop perfusion chamber, equilibrating to 37 °C, if using. Fetal and maternal peristaltic pumps with appropriate mani- fold tubing ftted to ensure pumps work within their midrange at 6 mL/min and 14 mL/min, respectively, with scope for fetal-side pumps to operate up to 12 mL/min, if investigating fow-mediated vasodilation (see Note 4). Hydrostatic pressure transducers, coupled to a pressure logger and computer with software installed for recording, with real- time screen readout. Gas cylinders and regulators to supply required levels of oxy- gen and carbon dioxide to perfusates. In-line oxygenator system for exchanging oxygen and carbon dioxide to required levels. In-line heat exchanger supplying heated water from a circulat- ing water bath for effective closed circuit perfusion if perform- ing closed-circuit perfusion. A bubble trap for each circuit to prevent non-soluble gases reaching the perfused tissue. A chamber ftted with an oxygen electrode or optode for each circuit to measure oxygen supply to the fetal villous microcir- culation and the maternal intervillous space, plus an additional Ex vivo Human Placental Perfusion 177 Fig. Depicting fetal-side (a) and maternal-side (b) perfusion, the capacity to measure real-time infow hydrostatic pressure as a measure of resistance to fow; pH, which is particularly important in closed-circuit perfusion, ppO2 in the fetal and maternal infow perfusate and the fetal venous perfusate, permitting a measure of tissue oxygen consumption and transfer. An alternative to an oxygenator is through-gassing a perfusate reservoir within a water bath using a sintered gassing tube (for open-circuit perfusion only). Options are available to recirculate perfusate in closed-circuit perfusion with reservoir sampling or send to waste in the open-circuit method with direct sampling. If using the benchtop perfusion system, two perfusate heat exchangers, or equivalent arrangement, one in each circuit, would need to be employed prior to the oxygenator; alternatively, all equipment may be housed within a heated cabinet arrangement to measure the partial pressure of oxygen in the fetal venous perfusate and gauge aerobic metabolism and transplacental oxygen transfer if relevant to the study. A further needle-type oxygen electrode/optode to assess intervillous space oxygen gradient mapping, sampled using a micromanipulator, if relevant to the study. A chamber ftted with a pH electrode for each circuit to enable pH adjustment if employing closed-circuit perfusion. Watch-makers’ forceps and Vannas scissors for chorionic plate arterial cannulation, forceps and fne pointed scissors for cho- rionic plate venous cannulation, straight fne Spencer-Well for- ceps for holding sutures, and standard scissors for trimming the placenta when mounted in the ring. Beakers to collect venous waste for disposal (open-circuit per- fusion) or reservoirs to collect and recirculate closed-circuit perfusate. Prepare perfusates according to individual requirements (see of Experimentation Subheading 2. Flow settings vary by center, but the range is 4–6 mL/min for the fetal circulation and 12–14 mL/min for the maternal cir- culation. Fetal-side circuit may increase by integers of 2 mL/ min if “fow-ramping” in vascular studies. Check that the hydrostatic pressure transducers are holding their calibration, using a column of water equivalent to 25 mmHg (circa 33. If necessary, recalibrate or perform spreadsheet correction factor on experimental results. In the absence of a placenta, perfuse the tubing in each circula- tory system with water, hold the experimental cannula at the experimental height position for the placenta, and record infow hydrostatic pressures for at least one revolution of the pumps. These data can be later used to correct for total resis- tance of the tubing with placenta following experimentation, to derive a representation of placental resistance alone. Prepare all dissection equipment, sutures, gauze, lab flm, and placenta clamping apparatus, so that time can be saved during cannulation and placental assembly on the day of perfusion. Liaise with research midwives/obstetric nurses for the recruit- ment of patients, as research volunteers, for the donation of their placentas. Switch on perfusate pumps, perfusion cabinet or circulating on Day water bath, reservoir water bath, hydrostatic pressure and O2 of Experimentation recording equipment, and aspirator pumps. Turn on gas regulators and employ gas to exchangers or through-gas reservoirs within water bath, according to design. Record time of birth, and once the placenta has been checked Collection, Inspection, for clinical purposes, transport to the laboratory within Cannulation, 15–20 min. Inspect the decidual surface to identify a lobule devoid of of Homeostasis breakages to the villous structure. Placing a gloved hand underneath the placenta, in contact with the chorionic plate, and rotating the placenta during inspection usually reveal fssured breaks in the decidua, which helps in the elucidation of septa damage and also decidual separation at the placenta margins. In all cases of damage, the villous tissue will appear as a rough texture and would incur a leakage from the fetopla- cental microcirculation into the intervillous space upon estab- 180 Paul Brownbill et al. If a suitable area is identifed, prime all perfusion tubing with perfusate, displacing the water with perfusate. For closed- circuit systems that will initially operate in an open-circuit manner, be sure to also prime current closed-circuit dead space. Turn the placenta over, to reveal the chorionic plate, and remembering lobule arrangements and tissue zones to be avoided where there are tears, select a pair of chorionic plate artery and veins, corresponding to the intact lobule and clear the plate of any blood using gauze swabs, in preparation for cannulation. Decide on where the suture point will be for the arterial can- nula to capture the zone of perfusion interest. Again, vascular anatomy exploration is key in determining the likelihood of perfusion into the desired and undesired zones. Make a small incision in the artery wall 1–2 cm afferent to the desired suture point. Using a 20 mL syringe, with fetal arterial cannula attached and primed with perfusate, insert the beveled end of the cannula into the lumen, being careful not to include air, and negotiate necessary branches, passing the desired suture point by at least 5 mm. The progression of the cannula through the artery can be aided by fushing the artery a little with the perfusate, which has the effect of expanding the vessel diameter. Suture around the vessel wall, being careful not to encounter villous tissue, or pierce the vessel wall, employing a double knot.

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Panels of biomarkers may be better than individual biomarkers to aid diagnosis generic 120mg starlix, but which combina- tions of biomarkers are likely to be of greatest use remains a matter of ongoing research buy starlix 120 mg without a prescription. Whichever biomarker(s) is used buy starlix 120mg line, levels must be interpreted in the con- text of the full clinical picture and never in isolation. The third international consensus defnitions for sepsis and septic shock (Sepsis-3). Surviving sepsis campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Serological reactions in pneumonia with a non-protein somatic fraction of pneumococcus. The physiological structure of human C-reactive protein and its complex with phosphocholine. Rheumatoid arthritis: national clinical guideline for management and treatment in adults. Acute phase reactants in infections: evidence-based review and a guide for clinicians. 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Comparison of diagnostic accuracy in sepsis between pre- sepsin, procalcitonin, and C-reactive protein: a systematic review and meta-analysis. The duration of hypotension before the initiation of antibiotic treatment is a critical determinant of survival in a murine model of Escherichia coli septic shock: association with serum lactate and infammatory cytokine levels. Early identifcation of intensive care unit-acquired infec- tions with daily monitoring of C-reactive protein: a prospective observational study. Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis. Procalcitonin as a prognostic and diagnostic tool for septic complications after major trauma. Procalcitonin, lipopolysaccharide-binding protein, interleukin-6 and C-reactive protein in community-acquired infections and sepsis: a prospec- tive study. 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Failure to reduce C-reactive protein levels more than 25% in the last 24 hours before intensive care unit discharge predicts higher in-hospital mortality: a cohort study. Early changes of procalcitonin may advise about prognosis and appropriateness of antimicrobial therapy in sepsis. Changes in circulating procalcitonin versus C-reactive pro- tein in predicting evolution of infectious disease in febrile, critically ill patients. The time course of blood C-reactive protein concentrations in relation to the response to initial antimicrobial therapy in patients with sepsis. C-reactive protein correlates with bacterial load and appropriate antibiotic therapy in suspected ventilator-associated pneumonia. Usefulness of consecutive C-reactive protein mea- surements in follow-up of severe community-acquired pneumonia. Procalcitonin versus C-reactive protein for guiding antibiotic therapy in sepsis: a randomized trial. 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