危重病患者血清细胞因子水平的动态变化及临床意义

目的 探讨危重患者血清细胞因子IL-6、TNF—α的动态变化及临床意义。方法 采用ELISA法测定35例危重患者IL-6及TNF—α的动态变化并与正常对照组进行比较。结果 35例患者血清IL-6、INF—α于24h内即显著升高，较正常对照组差异显著，以后呈波动性变化，于第6天出现第2次高峰。结论 细胞因子参与了SIRS向MODS的发生发展，IL-6、INF—α水平的变化对MoDs的诊断可能具有重要意义。     

Acetaminophen has limited antipyretic activity in critically ill patients

Purpose

Fever occurs commonly in the critically ill patients and may adversely affect outcome. Acetaminophen is one of the most commonly used antipyretic agents in the intensive care unit; however, there is little evidence that it is effective in this population. The objective of this study was to analyze the antipyretic activity of acetaminophen in critically ill patients.

Materials and Methods

We performed a retrospective study of medical intensive care unit and surgical intensive care unit patients with systemic inflammatory response syndrome and compared the resolution of fever in the presence and absence of acetaminophen treatment by comparing the absolute reduction in body temperature and the rate of cooling over comparable time frames in fevers that were untreated and those treated with acetaminophen.

Results

We analyzed 166 febrile episodes (body temperature, >38°C) in 59 patients with systemic inflammatory response syndrome without cancer, neurologic disease, or liver disease. Acetaminophen was administered for 88 of 166 fevers. Febrile episodes in which other antipyretic drugs or external cooling were administered were excluded. The response to acetaminophen was variable, but the absolute temperature reduction was slightly higher (mean, 0.86 versus 0.56°C; P = .0362), and the cooling rate was slightly more rapid (mean, 0.20 versus 0.13°C per hour; P = .0152) in acetaminophen-treated versus untreated fevers. There were no obvious differences between the most and least responsive patients.

Conclusions

We conclude that acetaminophen has significant albeit modest antipyretic activity in critically ill patients.     

Real-time monitoring of heart rate variability in critically ill patients

Purpose

Heart rate variability (HRV) is widely used to evaluate autonomic nervous function; however, real-time monitoring of HRV has rarely been attempted in the intensive care unit (ICU). We report our experience in performing real-time monitoring of HRV in our ICU.

Methods

We investigated 10 critically ill patients on total ventilatory support. Heart rate variability analysis was performed using the MemCalc system, which is a noninvasive, real-time analysis system. The low-frequency (LF) component of HRV reflects sympathetic and parasympathetic modulation, whereas the high-frequency (HF) component mainly reflects parasympathetic modulation. The LF/HF ratio represents a measure of sympathetic/parasympathetic balance.

Results

The HRV parameters for patients breathing spontaneously after extubation were significantly higher than those for patients on total ventilatory support. These findings suggest that mechanical ventilation under sedation may reduce autonomic nervous function in critically ill patients. In a representative case with septic shock, systolic blood pressure and LF/HF ratio showed a significant increase after intravenous infusion of epinephrine and then the HF component showed a significant increase due to vagal reflex.

Conclusions

The MemCalc system is practicable for real-time monitoring of HRV in the ICU. Heart rate variability parameters may offer useful information in the management of critically ill patients.     

Ciprofloxacin pharmacokinetics in critically ill patients: a prospective cohort study

Purpose

Optimal dosing of antibiotics is important for efficacy and avoidance of resistance. Fluoroquinolones are frequently used to treat severe infections in critically ill patients. We studied ciprofloxacin pharmacokinetics after administration of 400 mg twice a day (bid) intravenously (IV).

Material and methods

Serum concentrations were measured in 32 intensive care unit patients (age, 68.7 ± 17.4 years; Sepsis-related Organ Failure Assessment (SOFA) scores, 7.3 ± 3.4). Blood samples were drawn at 7 time points after ciprofloxacin infusion. We evaluated whether areas under the curve (AUCs) exceeded minimal inhibitory concentration (MIC) values of 0.125, 0.25, 0.5, 1.0, and 2.0 mg/L by 125 times and peak concentrations (C_max) 10 × MIC (C_max/MIC >10).

Results

The AUC/MIC more than 125 was achieved in 100% for MIC 0.125. For MIC values 0.25, 0.5, 1.0, and 2.0, results were 84%, 31%, 3%, and 0%, respectively (P < .01). The C_max/MIC more than 10 for MIC values of 0.125, 0.25, 0.5, 1.0, and 2.0 was realized in 100%, 97%, 69%, 25%, and 0%, respectively (P < .01). Female sex, SOFA_pulmonary points, and SOFA_renal points predicted higher AUC. Cumulative SOFA scores were most predictive of high AUCs.

Conclusions

Ciprofloxacin 400 mg bid IV leads to inadequate AUC/MIC and C_max/MIC ratios in many cases. Effective killing concentrations were only achieved in pathogens with MIC less than 0.25. As bacteria in intensive care unit patients often exceed this threshold, we recommend to use higher doses of ciprofloxacin (1200 mg daily) to ensure optimal bacterial killing and avoid antibiotic resistance.     

Pharmacokinetics and pharmacodynamics of dopamine and norepinephrine in critically ill head-injured patients

Objective To explore the pharmacokinetics and pharmacodynamics of dopamine and norepinephrine.Design Prospective, controlled, trial.Setting Neurosciences critical care unit.Patients Eight patients with a head injury, requiring dopamine or norepinephrine infusions to support cerebral perfusion pressure (CPP).Intervention Patients received in randomised order, either dopamine or norepinephrine to achieve and maintain a CPP of 70 mmHg, and then, following a 30-min period of stable haemodynamics, a CPP of 90 mmHg. Data were then acquired using the second agent. Haemodynamic measurements were made during each period and a blood sample was obtained at the end of each study period for analysis of plasma catecholamine concentrationsMeasurements and results Plasma levels of norepinephrine and dopamine were significantly related to infusion rates but did not have a simple linear relationship to haemodynamic parameters. However, there was a significant quadratic relationship between the infusion rate of dopamine and cardiac index (r ²=0.431), and systemic vascular resistance index (r ²=0.605), with a breakpoint (at which cardiac index reduced and SVRI increased) at a dopamine plasma level of ~ 50 nM/l (corresponding to an infusion rate of ~ 15 g·kg^-1·min^-1).Conclusions Norepinephrine and dopamine have predictable pharmacokinetics; however, those of dopamine do not fit a simple first-order kinetic model. The pharmacodynamic effects of dopamine and norepinephrine show much inter-individual variability and unpredictability. Plasma levels of dopamine appear to relate to variations in adrenergic receptor effects with break points that reflect expectations from infusion-rate related pharmacodynamics.     

Use of morphine cholescintigraphy in the diagnosis of acute cholecystitis in critically ill patients

Objective To determine the efficacy of morphine enhanced radionuclide cholescintigraphy (MC) in the diagnosis of acute cholecystitis (AC) in critically ill patients.Design Retrospective chart review.Setting 2 university hospitalsPatients and methods Records of all ICU patients who underwent MC as part of an evaluation for AC over an 8 year period were reviewed (n=45). All patients initially had standard radionuclide cholescintigraphy (RC) performed which showed nonvisualization of the gallbladder (GB) and were then given morphine sulfate (0.05–0.1 mg/kg iV).Results The mean age was 54 years (range 18–84 years). Risk factors for AC included fasting in 41 patients (mean 12.4 days) and total parenteral nutrition in 32 patients. Signs of biliary sepsis included temperature >100°F in 38 patients, WBC>10 000/ml³ in 40 patients, abdominal pain in 29 patients, and abnormal liver fuction tests in 42 patients. 23 patients had GB ultrasonography, with 7 showing stones. MC was positive (non-visualization) in 16 patients and negative (GB visualized) in 29, including 4 with gallstones. All patients in whom the GB was visualized did so within 1h. There were 13 patients with positive MC who underwent operation; 12 had AC (9 acalculous, 3 calculous). Three patients were treated medically and recovered (false positive). All 29 patients with negative MC were true negatives. Overall, MC had an accuracy of 91%, sensitivity of 100%, specificity of 88%, positive predictive value of 75%, and negative predictive value of 100%.Conclusion MC is a useful test in the evaluation of critically ill patients for suspected AC, particularly in patients with known risk factors or documented gallstones.Presented at the 22nd Annual Educational and Scientific Symposium of the Society of Critical Care Medicine, New York, NY, June 1993     

Polyneuropathies in critically ill patients: A prospective evaluation

Objective To determine the incidence, severity and course of polyneuropathies in patients with sepsis or systemic inflammatory response syndrome combined with multiple organ failure.Design Prospective study.Setting Division of Intensive Care Medicine of the Department of Anesthesiology and Intessive Care and Intensive Care Unit of the Department of Neurology, University Hospital Innsbruck, Austria.Patients Twenty-two patients between 23 and 77 years old with sepsis or systemic inflammatory response syndrome combined with multiple organ failure fulfilling strict inclusion and exclusion criteria.Interventions Clinical neurologic examination and electromyography/nerve conduction velocity measurements during the stay on the Intensive Care Unit and 2–3 months later.Measurements and results In 9 of the 22 patients signs of polyneuropathy were found at the initial clinical investigation and in 7 patients at the follow-up investigation. Electrophysiologic investigation revealed signs of polyneuropathy in 18 patients initially and in 11 patients 2–3 months later.Conclusion In our patient population the frequency of the development of polyneuropathy was high (81.8%). Electrophysiologic investigation is superior to clinical neurologic examination in the detection of polyneuropathies.     

Hypernatremia in critically ill patients

Hypernatremia is common in intensive care units. It has detrimental effects on various physiologic functions and was shown to be an independent risk factor for increased mortality in critically ill patients. Mechanisms of hypernatremia include sodium gain and/or loss of free water and can be discriminated by clinical assessment and urine electrolyte analysis. Because many critically ill patients have impaired levels of consciousness, their water balance can no longer be regulated by thirst and water uptake but is managed by the physician. Therefore, the intensivists should be very careful to provide the adequate sodium and water balance for them. Hypernatremia is treated by the administration of free water and/or diuretics, which promote renal excretion of sodium. The rate of correction is critical and must be adjusted to the rapidity of the development of hypernatremia.     

全身炎性反应综合征患者血清C反应蛋白、白细胞介素6和D-二聚体的变化

目的探讨神经科并发全身炎性反应综合征(SIRS)的危重症患者血清C-反应蛋白(CRP)、白细胞介素-6(IL-6)和D-二聚体(D-Di)水平变化及其与多器官功能障碍综合征(MODS)和病死率的关系。方法将120例神经科危重症患者根据是否并发SIRS分为SIRS组(48例)和非SIRS组(72例),分别于发病24 h内及3 d、7 d晨起空腹抽取静脉血5 mL,测定血清CRP、IL-6、D-Di水平,并观察两组患者的MODS发生率和病死率。结果发病24 h内、3 d、7 d不同时间血清CRP,非SIRS组内比较差异无统计学意义(P0.05),但SIRS组内比较差异有统计学意义(P0.05);各时间点SIRS组血清CRP水平明显高于非SIRS组(P0.01)。SIRS组发病24 h内、3 d、7 d时血清IL-6明显高于非SIRS组(P0.05)。非SIRS组发病24 h内、3 d、7 d不同时间D-Di水平比较差异无统计学意义(P0.05),SIRS组内比较差异有统计学意义(P0.05);各时间点SIRS组D-Di水平明显高于非SIRS组(P0.01)。SIRS组MODS发生率明显高于非SIRS组(χ2=5.042,P0.05),SIRS组病死率明显高于非SIRS组(χ2=7.879,P0.05)。结论血清CRP、IL-6及D-Di可作为预测MODS的早期指标。     

Hypophosphatemia in critically ill patients

Purpose

The aim of this study was to assess the association of phosphate concentration with key clinical outcomes in a heterogeneous cohort of critically ill patients.

Materials and Methods

This was a retrospective observational study at a general intensive care unit (ICU) of an Australian university teaching hospital enrolling 2730 adult critically ill patients.

Results

We studied 10?504 phosphate measurements with a mean value of 1.17 mmol/L (measurements every 28.8 hours on average). Hyperphosphatemia (inorganic phosphate [iP] concentration > 1.4 mmol/L) occurred in 45% and hypophosphatemia (iP ≤ 0.6 mmol/L) in 20%. Among patients without any episodes of hyperphosphatemia, patients with at least 1 episode of hypophosphatemia had a higher ICU mortality than those without hypophosphatemia (P = .004). In addition, ICU nonsurvivors had lower minimum phosphate concentrations than did survivors (P = .009). Similar results were seen for hospital mortality. However, on multivariable logistic regression analysis, hypophosphatemia was not independently associated with ICU mortality (adjusted odds ratio, 0.86 [95% confidence interval, 0.66-1.10]; P = .24) and hospital mortality (odds ratio, 0.89 [0.73-1.07]; P = .21). Even when different cutoff points were used for hypophosphatemia (iP ≤ 0.5, 0.4, 0.3, or 0.2 mmol/L), hypophosphatemia was not an independent risk factor for ICU and hospital morality. In addition, timing of onset and duration of hypophosphatemia were not independent risk factor for ICU and hospital mortality.

Conclusions

Hypophosphatemia behaves like a general marker of illness severity and not as an independent predictor of ICU or in-hospital mortality in critically ill patients.     

Hyperglycaemia and mortality in critically ill patients

Objective To describe hyperglycaemia as a possible marker of morbidity and mortality in critically ill medical and surgical patients admitted to a multidisciplinary ICU.Design Prospective cohort study.Setting A 13-bed non-cardiac multidisciplinary ICU in a university hospital.Patients and participants Adult patients consecutively admitted to the ICU in a 6-month period. Patients with fewer than 2 days stay in the ICU and patients with known diabetes were excluded.Measurements and results At admission a registration form was filled in including demographic data, first and second day APACHE II scores, infections and daily maximum blood glucose level. In surgical patients, high maximum blood glucose level during the stay in ICU was correlated with increased mortality, morbidity and frequency of infection. In medical patients, we found a non-significant trend towards a correlation between hyperglycaemia and morbidity and mortality, respectively.Conclusions High blood glucose level during the stay in ICU was a marker of increased morbidity and mortality in critically ill surgical patients. In medical patients the same trend was found, but non-significant. The population of patients in the present study are heterogeneous and the results from surgical critically ill patients should not be generalised to medical patients.     

Coagulation biomarkers in critically ill patients

This article discusses coagulation biomarkers in critically ill patients where coagulation abnormalities occur frequently and may have a major impact on the outcome. An adequate explanation for the cause is important, since many underlying disorders may require specific treatment and supportive therapy directed at the underlying condition. Deficiencies in platelets and coagulation factors in bleeding patients or patients at risk for bleeding can be achieved by transfusion of platelet concentrate or plasma products, respectively. Prohemostatic treatment may be beneficial in case of severe bleeding, whereas restoring physiological anticoagulant pathways may be helpful in patients with sepsis and disseminated intravascular coagulation.     

Endotoxin immunity and the developmentof the systemic inflammatory responsesyndrome in critically ill children

Background The systemic inflammatory response syndrome (SIRS) may be triggered by endotoxin. Humans have antibodies directed against the core of endotoxin (endotoxin core antibodies, EndoCAb) that appear to be protective following surgery and in sepsis. We hypothesised that children with elevated antibodies to endotoxin core would be less likely to develop SIRS in their initial period on intensive care. Because of the existing literature we defined two sub-groups according to the primary reason for ICU admission: infection and non-infection. Methods We recruited 139 consecutive patients admitted to a paediatric intensive care unit (PICU) with more than one organ failure for longer than 12 h as part of another study. Patients were classified on admission to PICU as having an infectious or a non-infections diagnosis. The occurrence of SIRS within 48 h of admission was recorded along with detailed clinical and demographic data, EndoCAb concentration and the potential confounding variables C-reactive protein and mannose-binding lectin. Results In the 71 patients admitted without infection (primarily post-operative and head injured) IgG EndoCAb was significantly lower in patients who developed SIRS than those who did not (72 vs. 131 MU/ml), independent of potential confounding variables. In patients with infection there was no significant difference in IgG EndoCAb between children developing SIRS and those who did not (111 vs. 80 MU/ml). Conclusion Head injured and post-operative patients admitted to PICU who develop early SIRS have significantly lower serum IgG EndoCAb levels than those who do not. M.W.T. and N.J.K. both act as scientific consultants for NatImmune, a Danish company exploring the therapeutic potential of MBL. M.G.M. is involved in the development of an anti-endotoxin vaccine This article refers to the editorial .     

Saccharomyces boulardii prevents diarrhea in critically ill tube-fed patients

Objective: To assess the preventive effect of Saccharomyces boulardii on diarrhea in critically ill tube-fed patients and to evaluate risk factors for diarrhea. Design: Prospective, multicenter, randomized, double-blind placebo-controlled study. Setting: Eleven intensive care units in teaching and general hospitals. Patients: Critically ill patients whose need for enteral nutrition was expected to exceed 6 days. Intervention: S. boulardii 500 mg four times a day versus placebo. Measurements and results: Diarrhea was defined by a semiquantitative score based on the volume and consistency of stools. A total of 128 patients were studied, 64 in each group. Treatment with S. boulardii reduced the mean percentage of days with diarrhea per feeding days from 18.9 to 14.2 % [odds ratio (OR) = 0.67, 95 % confidence interval (CI) = 0.50–0.90, P = 0.0069]. In the control group, nine risk factors were significantly associated with diarrhea: nonsterile administration of nutrients in open containers, previous suspension of oral feeding, malnutrition, hypoalbuminemia, sepsis syndrome, multiple organ failure, presence of an infection site, fever or hypothermia, and use of antibiotics. Five independent factors were associated with diarrhea in a multivariate analysis: fever or hypothermia, malnutrition, hypoalbuminemia, previous suspension of oral feeding, and presence of an infection site. After adjustment for these factors, the preventive effect of S. boulardii on diarrhea was even more significant (OR = 0.61, 95 % CI = 0.44–0.84, P < 0.0023). Conclusion: S. boulardii prevents diarrhea in critically ill tube-fed patients, especially in patients with risk factors for diarrhea. Received: 5 August 1996 Accepted: 23 january 1997     

Vancomycin clearance during continuous venovenous haemofiltration in critically ill patients

Objective: To study the pharmacokinetics of vancoymcin in critically ill patients with acute renal failure treated with continuous venovenous haemofiltration (CVVHF).¶Design: Open-label study.¶Setting: Hospital pharmacy centre and medical intensive care unit of the University Medical Centre Utrecht.¶Materials and methods: In a laboratory setting, the sieving coefficient (s) of vancomycin by polyacrilonitrile (PAN) haemofilters of different surface areas was studied. In one patient, the pharmacokinetics of vancomycin were studied following a single dose of vancomycin. Another patient was treated with a vancomycin dosing regimen based on data from the literature, but high trough concentrations made dose reduction necessary after 24 h of withholding therapy. After two doses of 250 mg, serum and ultrafiltrate samples were collected for pharmacokinetic evaluation.¶Intervention: CVVHF with the following operational characteristics: blood flow 200 ml/min, ultrafiltrate flow 25 ml/min, postdilution, PAN 06 hollow fibre haemofilter.¶Measurements and results: The average sieving coefficient in vitro was 0.73 ± 0.06, 0.86 ± 0.11, and 0.80 ± 0.06 for the PAN 03, 06, and 10 haemofilters, respectively. Changes in the sieving coefficient by increasing the ultrafiltration rate were not clinically significant. The first patient was given a single dose of vancomycin, 1000 mg by intravenous infusion. The following pharmacokinetic data were obtained: apparent volume of distribution (Vd) 55.8 l, terminal half-life time (t_{1/2 term}) 15.4 h, total clearance (Cl_tot) 2.5 l/h, CVVHF clearance (CL_{CVVHF, form 1}) 1.4 l/h, and body clearance (Cl_body) 1.1 l/h. The average sieving coefficient during the study period was 0.89 ± 0.03. In the second patient, the pharmacokinetics of vancomycin were studied following dose reduction: Vd 41.7 l, ¶t_{1/2 term} 20.3 h, Cl_tot 1.4 l/h, Cl_{CVVHF, form 1} 1.4 l/h, and Cl_body < 0.1 l/h. The average sieving coefficient during the study period was 0.88 ± 0.03. The cumulative amount of vancomycin removed by means of CVVHF during the 12-h study period was 245 mg in patient 1 and 228 mg in patient 2.¶Conclusion: CVVHF with a PAN 06 haemofilter effectively removed vancomycin in two critically ill patients. The amount of vancomycin removed with CVVHF was about 250 mg per 12 h. A clear difference in body clearance in the two patients was observed. Our dosage recommendation for vancomycin in critically ill patients receiving CVVHF is a loading dose of 15–20 mg/kg followed after 24 h by 250 to 500 mg twice daily with close monitoring of the serum and ultrafiltrate vancomycin concentration.     

Etiology of troponin elevation in critically ill patients

Purpose

The aim of this study was to assess the etiology of cardiac troponin elevation among patients admitted to the intensive care unit (ICU) and to examine whether etiology affects mortality and length of stay.

Methods

All patients admitted over 2 months underwent screening with troponin measurements and were included if 1 or more measurements were elevated. Two adjudicators retrospectively reviewed patient charts to determine the likely cause of troponin elevation.

Results

Of 103 patient admissions, 52 (50.5%) had 1 or more elevated troponin measurements, and 49 (94.2%) had medical charts available for review. Troponin elevation was adjudicated as myocardial infarction (MI) in 53.1% of patients, sepsis in 18.4%, renal failure in 12.2%, and other causes in 16.3%. Overall ICU mortality was 16.0%; 2.0% for patients with no troponin elevation, 23.1% in patients with MI, and 39.1% in patients with troponin elevation not due to MI. Having an elevated troponin level not due to MI was significantly associated with increased hospital mortality compared with having no troponin elevation.

Conclusions

The most common cause of troponin elevation among critically ill patients was MI. Patients with elevated troponin had worse outcomes compared with patients without troponin elevation, and troponin elevation not due to MI was predictive of increased hospital mortality.     

危重病患者全身应激对机体内环境的影响

目的 :探讨危重病患者应激状态下内环境的变化规律、代谢支持选择的最佳时机。方法 :12 7例因各种原因所致的全身炎症反应综合征 (SIRS)和多器官功能障碍综合征 (MODS) ,ICU危重病患者入院后 1、3、5、7、14日进行电解质、血糖、晶体渗透压监测 ,入院后第 2、5、10日检测血皮质醇。 38例接受重组人生长激素治疗。结果 :死亡组 (35例 )患者入院时表现为高钠血症和晶体渗透压升高 ,而存活组 (92例 )入院时出现低钠血症和晶体渗透压偏低 (P均 <0 .0 0 1)。死亡组患者血糖一直维持于较高水平 ,对胰岛素存在一定的耐受性 ;存活组患者治疗后血糖和胰岛素用量进行性下降 (P均 <0 .0 1)。生长激素能明显提高 2组患者血糖水平 (P均 <0 .0 1) ,增加危重病患者内环境紊乱。死亡组患者血皮质醇浓度一直处于较高水平 ,而存活组呈进行性下降至生理范围 (P<0 .0 1)。结论 :危重病患者应激反应可使内环境紊乱 ,这种紊乱与血皮质醇浓度及疾病的严重程度变化一致。血糖可作为危重症患者应激反应过程的一个监测指标。     

Posterior reversible encephalopathy syndrome (PRES) in critically ill obstetric patients

Objective To describe clinical, neuroradiological and evolutionary findings in obstetric patients with posterior reversible encephalopathy syndrome (PRES).Design Retrospective case series.Setting University intensive care unit (ICU).Patients Four critically ill patients. Two patients experienced PRES in late postpartum without the classical pre-eclamptic signs. All patients showed impairment of consciousness and epileptic seizures; two of them presented cortical blindness and headache, too. True status epilepticus (SE) occurred in two cases. In all patients MRI showed the typical feature of gray-white matter edema, mainly localized to the temporo-parieto-occipital areas.Interventions Normalization of high blood pressure (BP) and treatment of seizures. Two patients with SE and severe impairment of consciousness were treated with an intravenous valproate (ivVPA) bolus followed by continuous infusion.Measurements and results In three cases, neurological and MRI abnormalities completely resolved in about a week. Another patient died due to subarachnoid hemorrhage.Conclusion Posterior reversible encephalopathy syndrome is a well described clinical and neuroradiological syndrome characterized by headache, altered mental status, cortical blindness and seizures, and a diagnostic MRI picture; usually reversible, PRES can sometimes result in death or in irreversible neurological deficits, thus requiring early diagnosis and prompt treatment. PRES can have various etiologies, but pregnancy and postpartum more frequently lead to this condition. Treatment of seizures deserves special attention since the anti-epileptic drugs currently used in SE management may worsen vigilance as well as autonomic functions. Extensive research is needed to assess the role of ivVPA in this condition.     

Pharmacokinetics and absolute bioavailability of ciprofloxacin administered through a nasogastric tube with continuous enteral feeding to critically ill patients

Objective: To determine the pharmacokinetics and absolute bioavailability of ciprofloxacin in 12 critically ill patients receiving continuous enteral feeding. Design: a prospective, cross-over study. Setting: 12-bed surgical intensive care unit in a University Hospital. Patients: 12 stable critically ill patients on mechanical ventilation and receiving continuous enteral feeding (Normoréal fibres) without diarrhea or excessive residual gastric contents ( < 200 ml/4 h). None had gastro-intestinal disease, renal insufficiency (estimated creatinine clearance ≥ 50 ml/min) or was receiving medications that could interfere with ciprofloxacin absorption or metabolism. Measurements and main results: The study was carried out after the fourth (steady state) b. i. d. intravenous (i. v.) 1-h infusion of 400 mg and the second b. i. d. nasogastric (NG) dose of 750 mg (crushed tablet in suspension). Plasma concentrations were measured by high-performance liquid chromatography. The median (range) peak concentration after i. v. infusion was 4.1 (1.5–7.4) mg/l, and that after NG administration was 2.3 (0.7–5.8) mg/l, occurring 1.25 (0.75–3.33) h after dosing. The median [range] areas under plasma concentration-time curves were similar for the two administration routes (10.3 [3.3–34.6] and 8.4 [3.6–53.4] for i. v. infusion and NG administration, respectively). Ciprofloxacin bioavailability ranges from 31 to 82 % (median, 44 %). Conclusions: In tube-fed critically ill patients, a switch to the NG ciprofloxacin after initial i. v. therapy to simplify the treatment of severe infections is restricted to those for whom serial assessments of ciprofloxacin levels are routinely available. Received: 7 November 1997 Accepted: 8 July 1998