Clozapine-Induced Severe Toxicity: Exploring the Pharmacokinetic Profile of Clozapine and Its Significance in Hemodynamic Instability - A Case Report.

Hemodynamic instability in patients with clozapine intoxication can indirectly reflect the serum concentration of clozapine.We have described a case of a 32-year-old pregnant woman who developed life-threatening clozapine toxicity at 28 weeks of gestation. The levels of clozapine and norclozapine in the serum were high. We initiated hemoperfusion(HP) and other detoxification therapies to remove the drug. The patient had severely dilated peripheral blood vessels, which led to cardiac symptoms such as fatal hypotension and uncontrollable tachycardia, resulting in very high cardiac output and elevated Central venous oxygen saturation (ScvO2). Pharmacological intervention significantly improved the hemodynamics.In light of our observations in the ongoing case, we posit that evaluating hemodynamic parameters before and after blood detoxification could serve as a valuable means to gauge effectiveness and provide guidance for treatment.

The role of pulse indicator continuous cardiac output (PiCCO) and critical care ultrasound in volume status assessment during fluid resuscitation for and prognosis of septic shock patients.

Objectives: To investigate whether pulse index continuous cardiac output (PiCCO) and critical care ultrasound are highly consistent in volume status assessment during fluid resuscitation for septic shock patients and analyze their influence on the prognosis of septic shock. Methods: Eighty septic shock patients treated by Huizhou Central People's Hospital during December 2018 and December 2020 were included and divided into a study group and a control group by the presence of volume responsiveness, with each group having 40 patients. The control group was subject to PiCCO-guided fluid resuscitation therapy, while the study group was given fluid resuscitation therapy guided by critical care ultrasound. Cardiac output, cardiac function, and catheter-related infection (CRI) were documented for intergroup comparison to confirm whether these two techniques were consistent with each other regarding their effects on resuscitation for and prognosis of septic shock patients. Results: Mechanical ventilation duration (MVD) and intensive care unit (ICU) length of stay (LoS) were significantly shorter in the study group when compared with the control group, and the differences were statistically significant (p<0.05, respectively). In terms of blood pressure parameters, the two groups did not differ greatly in diastolic blood pressure (DBP), mean arterial pressure (MAP), systolic blood pressure (SBP), and central venous pressure (CVP) before resuscitation (p>0.05, respectively); at 6h(six hour) after resuscitation, DBP, MAP, SBP, and CVP were substantially increased in both groups as compared with the pre-resuscitation levels (all p<0.05), but the differences between the two groups lacked statistical significance (all p>0.05). Comparing urine volume and degrees of positive fluid balance at 6 h and 12 h after resuscitation, drastic increases in urine volume and positive fluid balance were observed in both groups at 12 h as compared with at 6 h (all p<0.05); nevertheless, the two groups showed no statistically significant difference in urine volume and positive fluid balance at 6 h or 12 h (p>0.05, respectively). With regards to prognosis, there was no statistically significant difference between the two groups in the number of cases of continuous renal replacement therapy (CRRT), dosage of vasoactive agents and 28-d mortality rate (all p>0.05). However, the incidence of CRI was markedly lower in the study group (0/40) as compared with the control group (5/40), and the difference was statistically significant (p<0.05). Conclusions: Both PiCCO and critical care ultrasound can help achieve favorable outcomes from resuscitation for septic shock patients. Compared with PiCCO, critical care ultrasound monitoring appears to be more effective in preventing CRI and reducing MVD and ICU LoS, thereby easing patients' medical burden.

CRRT influences PICCO measurements in febrile critically ill patients.

The aim of this study was to investigate whether continuous renal replacement therapy (CRRT) influences the global end-diastolic volume index (GEDVI), cardiac index (CI), and extravascular lung water index (EVLWI) measured by Pulse Index Continuous Cardiac Output (PICCO) in febrile patients. Fifteen fever patients were included in this study. CI, GEDVI, EVLWI, heart rate (HR), and mean arterial pressure (MAP) were measured at five time-points: before CRRT (T0), immediately after CRRT started (T1), 15 min after CRRT started (T2), immediately after CRRT stopped (T3), and 15 min after CRRT stopped (T4). Results have shown that CI and GEDVI were decreased significantly in T1 (CI: 4.09 ± 0.72 vs 2.81 ± 0.58 L/min m2, P = 0.000 and GEDVI: 727.86 ± 63.47 vs 531.07 ± 66.63 mL/m2, P = 0.000). However, CI and GEDVI were significantly increased in T3 (CI: 4.09 ± 0.72 vs 7.23 ± 1.32 L/min m2, P = 0.000 and GEDVI 727.86 ± 63.47 vs 1339.17 ± 121.52 mL/m2, P = 0.000). There were no significant differences in T2 and T4. Among the five-time points, no measurement errors were observed with regards to HR, MAP, and EVLWI. Therefore, the data herein contained suggests that PICCO measurements should begin 15 min after the start or stop of CRRT.

The effects of hemodynamic monitoring using the PiCCO system on critically ill patients.

OBJECTIVE: We aimed to evaluate the effects of hemodynamic monitoring using the pulse index continuous cardiac output (PiCCO) system with critically ill patients. METHODS: In total, 292 patients with primary physiological abnormalities of hypotension (n = 180) or hypoxemia (n = 112) were evaluated. The attending physicians completed a questionnaire before each catheterization. After each catheterization, the attending physicians reviewed each chart to determine the possibility of altering the therapy. RESULTS: In the hypotension subgroup, the attending physicians showed less accuracy in predicting the global end-diastolic index values (23.9%, 43/180), with a significant difference, and more accuracy in predicting the extravascular lung water index values (58.9%, 66/112), without a significant difference from the patients in the hypoxemia subgroup. In the hypotension patients, the lactate clearance rate within 6 h was significantly higher (36.4 ± 9.6 vs 21.3 ± 9.5; P<0.0001) when the hemodynamic monitoring led to therapeutic changes. CONCLUSIONS: The hemodynamic variables obtained using the PiCCO system improved the accuracy of the bedside evaluations and led to alterations in the therapeutic plans, particularly among the hypotension patients. The therapy changes showed no improvement in the overall mortality but were associated with improved tissue perfusion among the hypotension patients.

Clinical Application of Transabdominal Ultrasound Combined with PICCO in Septic Shock Fluid Resuscitation and Its Predictive Value for Survival Outcome.

To investigate the clinical value of transabdominal ultrasound combined with pulse index continuous cardiac output (PICCO) in fluid resuscitation of septic shock patients, and to analyze the predictive value of survival outcomes, 68 patients with septic shock were randomly divided into the ultrasound + PICCO group and PICCO group. Compared with before treatment, blood lactic acid (BLA) was cleared, and central venous pressure (CVP) and oxygenation index were significantly increased in all patients. The oxygen binding index, central venous oxygen saturation (ScVO2), and CVP in the ultrasound + PICCO group were increased compared with the PICCO group, while BLA, mechanical ventilation time, total fluid resuscitation input and hospitalization were significantly reduced. The extravascular lung water index and shape change index were positively correlated with sequential organ failure assessment. The combination of extravascular lung water index and shape change index had higher clinical value than each alone in predicting the death of patients with septic shock. The combination of transabdominal ultrasound with PICCO is better at guiding fluid resuscitation in patients with septic shock and has a certain predictive value with respect to the survival outcome of septic shock patients.

Application of pulse index continuous cardiac output system in elderly patients with acute myocardial infarction complicated by cardiogenic shock: A prospective randomized study.

BACKGROUND: Cardiogenic shock (CS) secondary to acute myocardial infarction (AMI) complicates management of the condition, and often leads to poor prognosis. Prompt and accurate monitoring of cardiovascular and accompanying hemodynamic changes is crucial in achieving adequate management of the condition. Advances in technology has availed procedures such as pulse index continuous cardiac output (PiCCO), which can offer precise monitoring of cardiovascular functions and hemodynamic parameters. In this study, PiCCO is evaluated for its potential utility in improving management and clinical outcomes among elderly patients with AMI complicated by CS. AIM: To assess whether use of the PiCCO system can improve clinical outcomes in elderly patients with AMI complicated by CS. METHODS: Patients from emergency intensive care units (EICU) or coronary care units (CCU) were randomized to receive PiCCO monitoring or not. The APACHE II score, SOFA score, hs-TnI, NT-proBNP, PaO2/FiO2 ratio and lactate levels on day 1, 3 and 7 after treatment were compared. The infusion and urine volume at 0-24 h, 24-48 h and 48-72 h were recorded, as were the cardiac index (CI), extravascular lung water index (EVLWI), intrathoracic blood volume index (ITBVI) and global end diastolic volume index (GEDVI) at similar time intervals. RESULTS: Sixty patients with AMI complicated by CS were included in the study. The PiCCO group had a significantly lower APACHE II score, SOFA score, hs-TnI and NT-proBNP levels on day 1, 3 and 7 after treatment. The infusion and urine volume during 0-24 h in the PiCCO group were significantly greater, and this group also showed significantly higher ADL scores. Furthermore, the PiCCO group spent lesser days on vasoactive agents, mechanical ventilation, and had a reduced length of stay in EICU/CCU. Additionally, the CI was significantly higher at 48 h and 72 h in the PiCCO group compared with that at 24 h, and the EVLWI, ITBVI and GEDVI were significantly decreased at 48 h and 72 h. CONCLUSION: Applying the PiCCO system could improve the clinical outcomes of elderly patients with AMI complicated by CS.

Utility of transpulmonary thermodilution with Pulse Index Continuous Cardiac Output system for hemodynamic assessment in a hemodialysis patient with arteriovenous fistula and continuous renal replacement therapy: A case report.

Close hemodynamic monitoring is crucial for the patients to guide cardiovascular therapy for the optimal management. Transpulmonary thermodilution offers a less invasive hemodynamic monitoring with Pulse Index Continuous Cardiac Output system analysis. Intracardiac shunts have been associated with well-defined alterations in transpulmonary thermodilution-related hemodynamic parameters leading to inaccurate measurements and therefore are among the contraindications for transpulmonary thermodilution. However, data on the effects of arteriovenous fistulas as well as extracorporeal circuits on the thermodilution curves remain limited and inconclusive. Herein, we report generation of modified thermodilution curve forms leading to incorrect calculation of thermodilution-derived hemodynamic parameters by Pulse Index Continuous Cardiac Output system in a female patient in the presence of Continuous Veno-Venous Hemodiafiltration and a high flow arteriovenous fistula. Our findings revealed generation of modified thermodilution curves and unacceptably high extravascular lung water readings by Pulse Index Continuous Cardiac Output system. This seems consistent with early recirculation of cold indicator in case of a peripheral shunt emphasizing the potential impact of high flow arteriovenous fistula on reliability of transpulmonary thermodilution measurements in critically ill patients, limiting the use of Pulse Index Continuous Cardiac Output system in these conditions.

Application of pulse index continuous cardiac output monitoring technology in treating severe craniocerebral injury complicating neurogenic pulmonary edema patients / 重庆医学

Objective To explore the application value of the pulse index continuous cardiac output monitoring technology (PICCO) in treating severe craniocerebral injury complicating neurogenic pulmonary edema(NPE).Methods Fifty-two cases of severe craniocerebral injury complicating NPE in the intensive care medicine department of this hospital were divided into the observation group and control group,26 cases in each group.The control group adopted the routine neurological treatment measures and guided the fluid infusion by monitoring the central venous pressure(CVP),while on the basis of the control group,the treatment group monitored the hemodynamics by PICCO and guided the fluid management according to the cardiac index(CI),extravascular lung water index (EVLWI),pulmonary vascular permeability index (PVPI),global end diastolic volume index(GEDVI) and intrathoracic blood volume index(ITBVI).The clinical curative effects,hemodynamic indexes,intracranial pressure(ICP),average daily infusion volume,mechanical ventilation time,hospital stay and GOS prognosis evaluation were compared between the two groups.Results The improvement of the heart rate(HR),mean arterial pressure (MAP),oxygenation index(PaO2/FiO2),ICP and other indicators in the observation group was more obvious than that in the control group(P＜0.05);the CVP rise in the control group was more obvious(P＜0.05);CI,EVLWI,PVPI,GEDVI and ITBVI in the observation group were improved and stabilized;the daily average infusion amount,mechanical ventilation time and hospital stay in the observation group were less than those in the control group(P＜0.05);but the good prognosis rate and mortality rate had no significant difference between the two groups(P＞0.05).Conclusion PICCO can better conduct the liquid management,improves the clinical symptoms,shortens the mechanical ventilation time and hospitalization stay,but the results show no significant improvement in prognosis and mortality.

Application strategy of PiCCO in septic shock patients.

Septic shock, also known as infectious or toxic shock, is a medical condition caused by severe infection and sepsis. Early identification, timely diagnosis and effective treatments are imperative to prevent this medical condition. The aim of the present study was to examine the application of pulse index continuous cardiac output (PiCCO) technique in the treatment of septic shock patients. Fifty septic shock patients were randomly divided into the conventional detection group (group C, n=25) and the PiCCO detection group (group P, n=25). A central venous catheter and radial artery catheter were placed into the patients of group C and a central venous catheter and PiCCO catheter (through femoral artery) were placed in the patients of group P to detect haemodynamics, which was managed and treated according to early goal-directed therapy (EGDT). PiCCO was applied to monitor and guide the application of fluid resuscitation, vasoconstriction drugs (dopamine) and positive inotropic drugs (dobutamine). The EGDT qualified rate of patients from the two groups at the 6th h of treatment, changes of post-resuscitation relevant parameters [blood lactate level, central venous oxygen saturation (ScvO2), central venous pressure (CVP), mean arterial pressure (MAP) and urine volume], positive fluid balance quantity and the dosage of dopamine and dobutamine at the 6th, 24th and 48th h were observed. In comparison to group C, group P showed an increase in the EGDT qualified rate and ScvO2 at the 6th h of treatment while the blood lactate level was decreased. The positive fluid balance quantity at the 6th and 24th h and the dosage of dobutamine were increased while the dosage of dopamine was reduced (P<0.05). There was no statistical significance in terms of the differences of positive fluid balance quantity and the dosage of dopamine and dobutamine in the two groups at the 48th h of treatment (P>0.05). There was also no statistical significance in terms of the differences of CVP, MAP and urine volume in the two groups (P>0.05). In conclusion, under the monitoring and guidance of the PiCCO technique, EGDT treatment should be applied to septic shock patients together with early fluid resuscitation and positive inotropic drugs instead of using only vasoconstriction drug, which cause elevation of blood pressure.

Value of detection of pentraxins 3 value combined with measurement of vascular lung water index in prognosis of patients with sepsis / 中华危重病急救医学

Objective To evaluate prognostic value of pentraxin3 (PTX3) content combining with extravascular lung water index (EVLWI) in patients with sepsis.Methods A retrospective analysis of complete clinical data of septic patients admitted to Department of Critical Care Medicine of the First Affiliated Hospital of Zhengzhou University from February 2013 to February 2014 was conducted.These patients were divided into two groups,survival group and death group,according to the outcome on the 28th day.Pulse index continuous cardiac output (PiCCO) was used to record the levels of EVLWI on the 1st,2nd and 3rd day of intensive care unit (ICU) admission.The plasma level of PTX3 was measured simultaneously by enzyme-linked immunosorbent assay (ELISA).At the same time,acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score and sequential organ failure assessment (SOFA) were calculated.Correlation analysis between plasma PTX3 and EVLWI values was performed,receiver operating characteristic curve (ROC) was drawn,and the prognostic value of each parameter was assessed finally.Results A total of 74 septic patients were enrolled,with 41 cases in the survival group and 33 cases in the non-survival group.Blood lactate,APACHE Ⅱ,SOFA scores in the non-survival group were significantly higher than those of the survival group at ICU admission,and the length of ICU stay was significantly shorter than that of the survival group,while differences of the other clinical characteristics between two groups were not statistically significant.The plasma PTX3 level gradually declined with time in both groups,and plasma PTX3 at 1,2,3 days after ICU admission in non-survival group were significantly higher than those in survival group [PTX3 (μg/L) at 1 day:46.3± 10.5 vs.19.4±6.5,t =-13.486,P =0.000; 2 days:34.8± 10.7 vs.17.7±8.4,t =-8.284,P =0.000; 3 days:23.9± 11.2 vs.15.6 ± 7.9,t =-5.036,P =0.000].EVLWI gradually declined in survival group,but increased in death group.EVLWI at 1,2,3 days after ICU admission in non-survival group were significantly higher than those in survival group [EVLWI (mL/kg) at 1 day:12.12 ± 4.31 vs.10.02 ± 2.87,t =-2.502,P =0.023; 2 days:13.67 ± 4.95 vs.9.08 ± 2.89,t =-5.188,P =0.000; 3 days:14.51±5.06 vs.8.09±2.50,t =-7.126,P =0.000].PTX3 at 1,2,3 days after ICU admission showed a significant positive correlation with EVLWI (r1 =0.747,r2 =0.719,r3 =0.705,all P =0.000).ROC curve analysis showed that the area under the ROC (AUC) of PTX3 at 1 day was 0.845 ± 0.045,at the cut-off point of 23.0 μg/L,PTX3 showed a sensitivity of 84.8％,a specificity of 74.1％,a negative predictive value of 85.81％,and a positive predictive value of 72.42％.AUC of EVLWI at 3 days was 0.838 ± 0.048,at the cut-off point of 10.5 mL/kg,EVLWI showed a sensitivity of 83.9％,a specificity of 82.9％,a negative predictive value of 86.45％,and a positive predictive value of 79.79％.Their sensitivities and specificities were found to be better than APACHE Ⅱ,SOFA score.AUC of PTX3 combined with EVLWI at 1 day was 0.886 ± 0.038.On the 1st day after ICU admission,with combination of the two indicators,cut-off point was found to be 0.312,a sensitivity of 86.8％,a specificity of 85.4％,a negative predictive value of 88.93％,and a positive predictive value of 82.72％.On the 3rd day after ICU admission,AUC of PTX3 combined with EVLWI was 0.856 ± 0.046,and showed a cut-off of 0.471 for the prognosis of sepsis,a sensitivity of 85.8％,a specificity of 85.4％,a negative predictive value of 87.97％,and a positive predictive value of 82.50％.Compared with other single index,a combination of above mentioned two indexes showed a better sensitivity and specificity.Conclusions PTX3 can serve as a novel prognostic indicator at early stage in septic patients.Combined with EVLWI,it shows important value in predicting prognosis of septic patients,and it also provides guidance in treatment of high-risk patients.