Drug-induced thrombocytopenia in the critically ill: a case-control study.

BACKGROUND: Drugs are suspected when obvious causes of intensive care unit (ICU)-acquired thrombocytopenia have been excluded. It has been estimated that 10% to 25% of cases may be drug induced. OBJECTIVES: The objectives of this study were to evaluate the risk of thrombocytopenia associated with drug classes commonly used in the ICU. METHODS: Data concerning patients admitted for more than 48 hours between 1997 and 2011 were extracted from a research-purpose database. Patients with thrombocytopenia within the first 72 hours of admission and with diagnoses or interventions considered strongly associated with thrombocytopenia were excluded. Drug exposures were compared and adjusted for confounders using conditional logistic regression. RESULTS: A total of 238 cases were identified after exclusions. Each case was matched according to sex, age, admission year, and admission unit with 1 control. In univariate analysis, quinolones (odds ratio [OR] = 1.56; 95% CI = 1.01-2.40) and extended spectrum ß-lactams (OR = 1.71; 95% CI = 1.00-2.93) were significantly associated with an increased risk of thrombocytopenia. After adjusting for confounders, exposure to quinolones was the only drug class with a statistically significant increase in risk of thrombocytopenia (OR = 1.697; 95% CI = 1.002-2.873; P = 0.049). CONCLUSION: In this study of ICU-acquired thrombocytopenia, we found no association between the exposures to several antibiotic classes, anticonvulsants, antiplatelet agents, nonsteroidal anti-inflammatory agents, and heparins and thrombocytopenia. As linezolid was not studied, no conclusions can be drawn concerning this agent. The statistically significant association between quinolones and thrombocytopenia warrants further investigation.

Thrombocytopenia in the critically ill: prevalence, incidence, risk factors, and clinical outcomes.

PURPOSE: The aim of this cohort study was to describe the prevalence, incidence, and risk factors for thrombocytopenia in the intensive care unit (ICU) and to evaluate the impact of thrombocytopenia on mortality with further comparisons amongst major diagnostic categories. METHODS: Patients admitted to the ICU from 1997-2011 for cardiac, medical, surgical, and trauma conditions were included. The presence of a platelet count < 100 × 10(9)·L(-1) on admission day or its appearance during ICU stay were considered as prevalent and incident thrombocytopenia, respectively. Risk factors for thrombocytopenia and the influence of thrombocytopenia on mortality were also analyzed. RESULTS: This study included 20,696 patients. Prevalent and incident thrombocytopenia occurred in 13.3% and 7.8% of patients, respectively, with associated mortality rates of 14.3% and 24.7%, respectively, compared with 10.2% in the group with normal platelet count (P < 0.001). After adjustments, thrombocytopenia remained associated with an increased risk of mortality (odds ratio 1.25; 95% confidence interval 1.20 to 1.31; P < 0.001). The greatest impact of thrombocytopenia on mortality was observed in the cancer, respiratory, digestive, genitourinary, and infectious diagnostic categories. Independent risk factors included age, female sex, admission platelet counts and hemoglobin, mechanical ventilation, days of hospitalization prior to ICU admission, liver cirrhosis, hypersplenism, coronary bypass grafting, intra-aortic balloon pump placement, acute hepatitis, septic shock, and pulmonary embolism or deep vein thrombosis. CONCLUSIONS: Thrombocytopenia in the ICU is associated with an independent risk of mortality that varies greatly depending on diagnostic admission category.

Effect of ventilatory variability on occurrence of central apneas.

OBJECTIVE: To compare the influence of 2 ventilation strategies on the occurrence of central apneas. METHODS: This was a prospective, comparative, crossover study with 14 unsedated subjects undergoing weaning from mechanical ventilation in the medical ICU of Hôpital du Sacré-Cœur, Montréal, Québec, Canada. The subjects were ventilated alternately in neurally adjusted ventilatory assist (NAVA) and pressure support ventilation (PSV) modes. Inspiratory flow/time and pressure/time waveforms and diaphragmatic electrical activity were used to detect central apneas. Ventilatory variability and breathing pattern were evaluated in both modes. Breathing patterns just before central apneas, and associations between apneas and sleep patterns (electroencephalogram) were studied. RESULTS: Switching from PSV to NAVA did not change mean minute ventilation, tidal volume, or breathing frequency. However, tidal volume variability, defined as the coefficient of variability (standard error/mean), was significantly greater with NAVA than with PSV (17.2 ± 8 vs 10.3 ± 4, P = .045). NAVA induced a greater decrease in central apneas, compared to PSV (to 0 with NAVA vs 10.5 ± 11 with PSV, P = .005). Central apneas during PSV were detected only during non-rapid-eye-movement sleep. CONCLUSIONS: NAVA was associated with increased ventilatory variability, compared to constant-level PSV. With NAVA the absence of over-assistance during sleep coincided with absence of central apneas, suggesting that load capacity and/or neuromechanical coupling were improved by NAVA and that this improvement decreased or abolished central apneas.

Sleep quality in mechanically ventilated patients: comparison between NAVA and PSV modes.

BACKGROUND: Mechanical ventilation seems to occupy a major source in alteration in the quality and quantity of sleep among patients in intensive care. Quality of sleep is negatively affected with frequent patient-ventilator asynchronies and more specifically with modes of ventilation. The quality of sleep among ventilated patients seems to be related in part to the alteration between the capacities of the ventilator to meet patient demand. The objective of this study was to compare the impact of two modes of ventilation and patient-ventilator interaction on sleep architecture. METHODS: Prospective, comparative crossover study in 14 conscious, nonsedated, mechanically ventilated adults, during weaning in a university hospital medical intensive care unit. Patients were successively ventilated in a random ordered cross-over sequence with neurally adjusted ventilatory assist (NAVA) and pressure support ventilation (PSV). Sleep polysomnography was performed during four 4-hour periods, two with each mode in random order. RESULTS: The tracings of the flow, airway pressure, and electrical activity of the diaphragm were used to diagnose central apneas and ineffective efforts. The main abnormalities were a low percentage of rapid eye movement (REM) sleep, for a median (25th-75th percentiles) of 11.5% (range, 8-20%) of total sleep, and a highly fragmented sleep with 25 arousals and awakenings per hour of sleep. Proportions of REM sleep duration were different in the two ventilatory modes (4.5% (range, 3-11%) in PSV and 16.5% (range, 13-29%) during NAVA (p = 0.001)), as well as the fragmentation index, with 40 ± 20 arousals and awakenings per hour in PSV and 16 ± 9 during NAVA (p = 0.001). There were large differences in ineffective efforts (24 ± 23 per hour of sleep in PSV, and 0 during NAVA) and episodes of central apnea (10.5 ± 11 in PSV vs. 0 during NAVA). Minute ventilation was similar in both modes. CONCLUSIONS: NAVA improves the quality of sleep over PSV in terms of REM sleep, fragmentation index, and ineffective efforts in a nonsedated adult population.

Protective vascular treatment of patients with peripheral arterial disease: guideline adherence according to year, age and gender.

OBJECTIVES: To evaluate vasoprotective pharmacological treatment of patients with peripheral arterial disease (PAD) according to: 1) year, 2) age and 3) gender. METHODS: An observational retrospective study was conducted to evaluate the systemic vascular treatment of a population-based cohort of patients with PAD > or = 50 years old, discharged from a tertiary-care teaching hospital between January 1, 1997 and December 11, 2006. Data were obtained from the Régie de l'assurance maladie du Québec. Drugs evaluated included antiplatelet agents (APs), statins (STs) and angiotensin converting enzyme inhibitors (ACEIs), and a combination of all three. Proportions of patients treated were compared according to year, age and gender using Chi-square. RESULTS: The mean age of the study population (5962 individuals) was 73.2 +/- 9.1 years; 43.8% were women. After hospital discharge, 71.6%, 47.6%, 42.2% and 20.6% were taking respectively, an AP, statin, ACEI or all three. Protective treatment improved significantly from 1997 to 2006. Significantly more subjects 50-64 years used a statin or all three agents, compared to subjects > or = 65 years (statins: 56.6% vs. 45.8%, all three: 26.2% vs. 19.5%; p < 0.001). Significantly more men than women used statins (49.1% vs. 45.6%; p < 0.001) and ACEIs (44.5% vs. 39.3%; p < 0.001). Similarily, use of all three agents was 22.4% for men and 18.2% for women (p < 0.001). CONCLUSIONS: Although systemic vascular treatment received by patients with PAD has increased in the past years, it remains suboptimal, particularly for older patients and women. Strategies to improve adherence to treatment guidelines should be developed for these high-risk populations.

Pain management after tonsillectomy: morphine is not enough.

INTRODUCTION: Tonsillectomy is usually done as day surgery, transferring to the parents most of the postoperative care. They often feel alone and incompetent in front of a child in pain. We developed a guide to help parents for both the evaluation and the management of postoperative pain. OBJECTIVE: To improve pediatric posttonsillectomy pain management with the implementation of a parental guide and treatment algorithm. METHODS: Eighty children (5-17 years) were recruited in this randomized clinical trial. Parents and children were assigned to one of the research groups: control or experimental. All received an identical prescription for acetaminophen (15 mg/kg) and morphine (0.3 mg/kg), information about the medication, a visual analogue scale (VAS), and index cards to be filled at home. The experimental group also received a treatment algorithm associating pain scores with analgesics. RESULTS: Pain scores for the control group and the experimental group were 5.3 and 4.7 on the day of surgery, 4.0 and 3.6 the next day, 2.2 and 2.3 3 days later, and 1.6 and 1.4 1 week after the intervention, respectively. The side effects and the analgesics given were comparable for both groups. CONCLUSION: No significant difference was demonstrated for the studied parameters, probably because the majority of the parents followed the prescriptions well. The guide was much appreciated. The children understood the VAS easily and liked using it. The combination of acetaminophen-morphine needs to be revisited since pain remains problematic.

Technical report: optimal quantity of saline for epidural pressure waveform analysis.

PURPOSE: Epidural waveform analysis (EPWA) is a simple test to confirm the optimal placement of an epidural catheter. It relies on the transmission of the thecal pressure waveform through the epidural catheter. Little is known about the optimal volume of catheter injectate needed to optimize the EPWA test. METHODS: In a randomized controlled trial we compared three different catheters: stimulating, open-ended hole [S1]; stimulating, three-hole [S3]; non-stimulating three-hole [NS3]) in 60 patients in an unblinded pilot study. After catheter insertion using a loss of resistance to air technique, we recorded the dose response curve of EPWA and the presence of epidural pressure wave transmitted through the catheter to repeated injections of 2.5 mL saline boluses in the catheter to a total volume of 10 mL. All patients were followed by the acute pain service to confirm adequacy of postoperative epidural analgesia. RESULTS: The S3 catheters were significantly more responsive (able to transmit a pulsatile waveform) compared to the S1 [P = 0.003 (S3) and P = 0.012 (NS3)] at low injectate volume, while there was no differences between the S3 catheters in their ability to transmit a waveform for EPWA (P = 0.25). There was no increase in responsiveness after 2.5 mL injected for S3 catheters and 5 mL for the S1 catheter. Three patients had soft catheters that did not transmit an epidural pulsative waveform. CONCLUSIONS: For EPWAs, S3 epidural catheters are superior to S1 catheters for determining pulsative waveform transmission at low injectate volume. The optimal initial quantity of saline for EPWA is 5 mL regardless of the catheter type used.

Feasibility of extended use of an electromagnetic lithotripter beyond the manufacturer's recommended maintenance schedule.

OBJECTIVES: The study evaluates the effect of chronic usage, beyond the recommended maintenance schedule, on the efficacy of electromagnetic lithotripter. To our knowledge, there is no publication investigating the effect of chronic usage on the electromagnetic lithotripter, despite the maintenance schedule established by the manufacturers. Our goal is to verify if the acoustic parameters of the shock wave changed with usage, and if this change could be associated with change in clinical efficacy. METHODS: This study lasted 18 months. Every 6 months the lithotripter's efficacy was evaluated in two ways: objectively and clinically. Objective efficacy was measured using a piezoelectric hydrophone and artificial stones to capture the acoustic parameters and the crater of fragmentation, respectively. Clinical efficacy data was collected by studying the rate of successful extracorporeal shock wave lithotripsy treatment in patients with urolithiasis. The changes in clinical efficacy, acoustic parameters, and craters of fragmentation were compared and analyzed with appropriate statistical methods. RESULTS: Five hundred twenty five patients participated in the study. The clinical efficacy remained stable throughout the three observation periods (55.7%, 66.2% and 55.5%; p = 0.11). The focal head of the lithotripter was used three times the recommended schedule. There was no obvious change in the acoustic parameters of the shock waves, and the focal zone remained stable. CONCLUSIONS: The clinical efficacy of the electromagnetic lithotripter appears to be stable despite usage beyond the recommended maintenance schedule. More studies are needed to validate the safety of this practice.

A prospective comparative study of two indirect methods for confirming the localization of an epidural catheter for postoperative analgesia.

We prospectively evaluated, in randomized order, 2 indirect methods of confirming the localization of an epidural catheter for postoperative analgesia in 218 surgical patients: epidural stimulation test (EST) and epidural pressure waveform analysis (EPWA). The epidural space was localized by using a loss of resistance technique. All catheters were inserted 5 cm into the epidural space and primed with 5 mL of 0.9% normal saline. There were no differences between the methods: the positive predictive value and specificity were high (100% in both groups), but the sensitivity was moderate (80% for EST and 81% for EPWA) and the negative predictive value was low (16% for EST and 17% for EPWA). Combining both methods yielded better sensitivity (97%) and negative predictive value (57%) (P < 0.001). The sensitivity of EST was increased to 87% (P < 0.05) if sensory response was included as well as motor response for stimulation less than 10 mA. We suggest the inclusion of sensory response in the appropriate dermatome at a current <10 mA as a criterion for adequate epidural catheter localization for EST testing. EPWA sensitivity was significantly better with older patients: 94% for patients older than 80 yr compared with 63% for patients younger than 40, 73% for patients 40 to 60, and 85% for patients aged 60 to 80 yr (P = 0.03). We conclude that the two tests are comparable for confirming catheter placement.

[Severe bradycardia and asystole with low dose sufentanil during induction with sevoflurane: a report of three cases]. / Bradycardie sévère et asystolie lors d'induction au sévoflurane et sufentanil à faible dose: à propos de trois cas.

OBJECTIVES: In a randomized double blind clinical study using low doses of fentanyl or sufentanil during sevoflurane induction, we observed three cases of severe bradycardia, forcing us to discontinue the study. We wish to describe these three cases. CLINICAL DATA: Anesthesia was induced in the three patients, using a single breath technique consisting of a mixture of sevoflurane 8% with a nitrous oxide flow of 3 L x min(-1) and an oxygen flow of 3 L x min(-1). After the patients had lost consciousness, low dose sufentanil was administered (0.025 microg x kg(-1) for the first patient and 0.1 microg x kg(-1) for the other two patients). Heart rate fell to 38, 40 and 42 beats x min(-1) respectively two minutes after the sufentanil injection in these three patients, and progressed to asystole in the third. All the patients responded to atropine 0.6 mg i.v. CONCLUSION: The addition of sufentanil, even at very low doses, during anesthesia induction with sevoflurane using a single breath technique, may be dangerous because of possible bradycardia and even asystole.