Giovanni Mistraletti

Analgesia and functional outcome after total knee arthroplasty: periarticular infiltration vs continuous femoral nerve block

BACKGROUND Capacity to ambulate represents an important milestone in the recovery process after total knee arthroplasty (TKA). The purpose of this study was to determine the analgesic effect of two analgesic techniques and their impact on functional walking capacity as a measure of surgical recovery. METHODS Forty ASA II-III subjects undergoing TKA were enrolled in a randomized, double-blind, single-centre study receiving 48 h postoperative analgesia with either periarticular infiltration of local anaesthetic (Group I) or continuous femoral nerve block (Group F). Breakthrough pain relief was achieved with patient-controlled analgesia (PCA) morphine. The main outcome was postoperative morphine consumption. Early (postoperative days 1-3) and late (6 weeks) functional walking capacity (2 and 6 min walk tests, 2MWT and 6MWT, respectively), degree of physical activity (CHAMPS), health-related quality of life (SF-12), and clinical indicators of knee function (WOMAC, Knee Society evaluation, and range of motion) were measured. RESULTS Patients in Group F used the PCA less (P=0.02) to achieve adequate analgesia. Postoperative 2MWT was similar in both groups (P=0.27). Six weeks after surgery, recovery of 6MWT, physical activity, and knee function were significantly improved in Group F (P<0.05). Preoperative walking capacity, physical activity and early total walking time were the independent predictors of early recovery. Distance and time spent walking were the predictors of functional walking exercise capacity at 6 weeks after surgery. CONCLUSIONS Femoral block is associated with lower opioid consumption and a better recovery at 6 weeks than periarticular infiltration. Early postoperative activity measures (2MWT and walking time) were proved to be possible indicators of knee function recovery at 6 weeks after surgery.

Intraoperative Esmolol Infusion in the Absence of Opioids Spares Postoperative Fentanyl in Patients Undergoing Ambulatory Laparoscopic Cholecystectomy

BACKGROUND:The use of opioids during ambulatory surgery can delay hospital discharge or cause unexpected hospital admission. Preliminary studies using an intraoperative continuous infusion of esmolol in place of an opioid have inconsistently reported a postoperative opioid-sparing effect. In this study, we compared esmolol versus either intermittent fentanyl or continuous remifentanil on postoperative opioid-sparing, side effects, and time of discharge. METHODS:Ninety patients (consisting of three groups) were enrolled in this prospective, randomized, and observer-blinded study. The control group (n = 30) received intermittent doses of fentanyl, the esmolol group (n = 30) received a continuous infusion of esmolol (5–15 &mgr;g · kg−1 · min−1) and no supplemental opioids during surgery, and the remifentanil group (n = 30) received a continuous infusion of remifentanil (0.1–0.5 &mgr;g · kg−1 · min−1). General anesthesia was standardized, and adjuvant medications included acetaminophen, ketorolac, local anesthetics in the skin incisions, dexamethasone, and droperidol. Postoperative analgesia included fentanyl. RESULTS:The amount of fentanyl in the postanesthesia care unit was significantly less in the esmolol group, 91.5 ± 42.7 &mgr;g, compared with the other two groups, remifentanil, 237.8 ± 54.7 &mgr;g, control, 168.1 ± 96.8 &mgr;g (P < 0.0001). The incidence of nausea was more frequent in the control (66.7%) and remifentanil (67.9%) groups compared with the esmolol group (30%) (P < 0.01). The esmolol group reached the White-Song score of 12 of 14 faster than the remifentanil group (P < 0.01), and left the hospital 45–60 min earlier (P < 0.004). CONCLUSIONS:Intraoperative IV infusion of esmolol contributes to a significant decrease in postoperative administration of fentanyl and ondansetron and facilitates earlier discharge.

Volume of activity and occupancy rate in intensive care units. Association with mortality

ObjectiveMortality after many procedures is lower in centers where more procedures are done. It is controversial whether this is true for intensive care units, too. We examined the relationship between the volume of activity of intensive care units (ICUs) and mortality by a measure of risk-adjusted volume of activity specific for ICUs.DesignProspective, multicenter, observational study.SettingEighty-nine ICUs in 12 European countries.PatientsDuring a 4-month study period, 12,615 patients were enrolled.InterventionsDemographic and clinical statistics, severity at admission and a score of nursing complexity and workload were collected.ResultsTotal volume of activity was defined as the number of patients admitted per bed per year, high-risk volume as the number of high-risk patients admitted per bed per year (selected combining of length of stay and severity of illness). A multi-step risk-adjustment process was planned. ICU volume corresponding both to overall [odds ratio (OR) 0.966] and 3,838 high-risk (OR 0.830) patients was negatively correlated with mortality. Relative mortality decreased by 3.4 and 17.0% for every five extra patients treated per bed per year in overall volume and high-risk volume, respectively. A direct relationship was found between mortality and the ICU occupancy rate (OR 1.324 and 1.351, respectively).ConclusionsIntensive care patients, whatever their level of risk, are best treated where more high-risk patients are treated. Moreover, the higher the ICU occupancy rate, the higher is the mortality.

Diaphragm ultrasound as indicator of respiratory effort in critically ill patients undergoing assisted mechanical ventilation: a pilot clinical study

IntroductionPressure-support ventilation, is widely used in critically ill patients; however, the relative contribution of patient’s effort during assisted breathing is difficult to measure in clinical conditions. Aim of the present study was to evaluate the performance of ultrasonographic indices of diaphragm contractile activity (respiratory excursion and thickening) in comparison to traditional indices of inspiratory muscle effort during assisted mechanical ventilation.MethodConsecutive patients admitted to the ICU after major elective surgery who met criteria for a spontaneous breathing trial with pressure support ventilation were enrolled. Patients with airflow obstruction or after thoracic/gastric/esophageal surgery were excluded. Variable levels of inspiratory muscle effort were achieved by delivery of different levels of ventilatory assistance by random application of pressure support (0, 5 and 15 cmH2O). The right hemidiaphragm was evaluated by B- and M-mode ultrasonography to record respiratory excursion and thickening. Airway, gastric and oesophageal pressures, and airflow were recorded to calculate indices of respiratory effort (diaphragm and esophageal pressure–time product).Results25 patients were enrolled. With increasing levels of pressure support, parallel reductions were found between diaphragm thickening and both diaphragm and esophageal pressure–time product (respectively, R = 0.701, p < 0.001 and R = 0.801, p < 0.001) during tidal breathing. No correlation was found between either diaphragm or esophageal pressure–time product and diaphragm excursion (respectively, R = −0.081, p = 0.506 and R = 0.003, p = 0.981), nor was diaphragm excursion correlated to diaphragm thickening (R = 0.093, p = 0.450) during tidal breathing.ConclusionsIn patients undergoing in assisted mechanical ventilation, diaphragm thickening is a reliable indicator of respiratory effort, whereas diaphragm excursion should not be used to quantitatively assess diaphragm contractile activity.

Oxygen consumption is depressed in patients with lactic acidosis due to biguanide intoxication

IntroductionLactic acidosis can develop during biguanide (metformin and phenformin) intoxication, possibly as a consequence of mitochondrial dysfunction. To verify this hypothesis, we investigated whether body oxygen consumption (VO2), that primarily depends on mitochondrial respiration, is depressed in patients with biguanide intoxication.MethodsMulticentre retrospective analysis of data collected from 24 patients with lactic acidosis (pH 6.93 ± 0.20; lactate 18 ± 6 mM at hospital admission) due to metformin (n = 23) or phenformin (n = 1) intoxication. In 11 patients, VO2 was computed as the product of simultaneously recorded arterio-venous difference in O2 content [C(a-v)O2] and cardiac index (CI). In 13 additional cases, C(a-v)O2, but not CI, was available.ResultsOn day 1, VO2 was markedly depressed (67 ± 28 ml/min/m2) despite a normal CI (3.4 ± 1.2 L/min/m2). C(a-v)O2 was abnormally low in both patients either with (2.0 ± 1.0 ml O2/100 ml) or without (2.5 ± 1.1 ml O2/100 ml) CI (and VO2) monitoring. Clearance of the accumulated drug was associated with the resolution of lactic acidosis and a parallel increase in VO2 (P < 0.001) and C(a-v)O2 (P < 0.05). Plasma lactate and VO2 were inversely correlated (R2 0.43; P < 0.001, n = 32).ConclusionsVO2 is abnormally low in patients with lactic acidosis due to biguanide intoxication. This finding is in line with the hypothesis of inhibited mitochondrial respiration and consequent hyperlactatemia.

Functional walking capacity as an outcome measure of laparoscopic prostatectomy: the effect of lidocaine infusion

BACKGROUND Intravenous lidocaine infusion has been shown to affect postoperative pain intensity. This present study was performed to assess the effect of intra- and postoperative lidocaine infusion on postoperative functional walking capacity, as a measure of surgical recovery. METHODS Forty patients undergoing laparoscopic prostatectomy were randomized to receive an i.v. infusion of either lidocaine 2 mg kg(-1) h(-1) during surgery and 1 mg kg(-1) min(-1) for the first 24 postoperative hours (lidocaine group) or an equivalent volume of saline 0.9% (control group). All patients received postoperative patient-controlled analgesia with i.v. morphine. Primary outcome was functional walking capacity, as assessed by distance attained during the 2 min walking test (2MWT), recorded daily for the first 3 postoperative days. Morphine consumption and pain intensity were recorded. RESULTS 2MWT distance decreased by an average of 60% (P<0.01) in both groups on postoperative day 1 (from 150 m before surgery to 53 m), but the decrease was 26 m less in the lidocaine group (P=0.009). During postoperative days 2 and 3, the 2MWT distance increased to an average of 96 m, still 30% less than the preoperative values. There was a significant negative correlation on postoperative days 1 and 2 between the 2MWT distance, pain intensity and fatigue, and morphine consumption. Lidocaine infusion was an independent predictor of the degree of postoperative decrease in 2MWT distance. More patients in the lidocaine group were free from PCA on the second postoperative day (P=0.011). CONCLUSIONS Infusion of lidocaine during surgery and for the first postoperative day attenuated the deterioration in functional walking capacity, and had an opioid sparing effect.

Metformin overdose causes platelet mitochondrial dysfunction in humans

IntroductionWe have recently demonstrated that metformin intoxication causes mitochondrial dysfunction in several porcine tissues, including platelets. The aim of the present work was to clarify whether it also causes mitochondrial dysfunction (and secondary lactate overproduction) in human platelets, in vitro and ex vivo.MethodsHuman platelets were incubated for 72 hours with saline or increasing doses of metformin (in vitro experiments). Lactate production, respiratory chain complex activities (spectrophotometry), mitochondrial membrane potential (flow-cytometry after staining with JC-1) and oxygen consumption (Clark-type electrode) were then measured. Platelets were also obtained from ten patients with lactic acidosis (arterial pH 6.97 ± 0.18 and lactate 16 ± 7 mmol/L) due to accidental metformin intoxication (serum drug level 32 ± 14 mg/L) and ten healthy volunteers of similar sex and age. Respiratory chain complex activities were measured as above (ex vivo experiments).ResultsIn vitro, metformin dose-dependently increased lactate production (P < 0.001), decreased respiratory chain complex I activity (P = 0.009), mitochondrial membrane potential (P = 0.003) and oxygen consumption (P < 0.001) of human platelets. Ex vivo, platelets taken from intoxicated patients had significantly lower complex I (P = 0.045) and complex IV (P < 0.001) activity compared to controls.ConclusionsDepending on dose, metformin can cause mitochondrial dysfunction and lactate overproduction in human platelets in vitro and, possibly, in vivo.Trial registrationNCT%2000942123.

Scoring system for the selection of high-risk patients in the intensive care unit.

Objective:Patients admitted to the intensive care unit greatly differ in severity and intensity of care. We devised a system for selecting high-risk patients that reduces bias by excluding low-risk patients and patients with an early death irrespective of the treatment. Design:A posteriori analysis of a multiple-center prospective observational trial. Setting:A total of 89 units from 12 European countries, with 12,615 patients. Intervention:Demographic and clinical data: severity of illness at admission, daily score of nursing workload, length of stay, and hospital mortality. Methods:We enrolled patients with intensive care unit length of stay of >24 hrs. Three groups of high-risk patients were created: a) Severity group, those with Simplified Acute Physiology Score (SAPS II) over the median; b) Intensity-of-care group, patients with >1 day of high level of care (assessed by logistic analysis); and c) MIX group, patients fulfilling both Severity and Intensity-of-care criteria. The groups were included in a logistic regression model (random split-sample design) to identify the characteristics associated with hospital mortality. We compared the outcome prediction of the SAPS II model (unsplit sample) against our model. Main Results:Out of 8,248 patients, the Severity method selected 3,838 patients, Intensity-of-care selected 4,244, and both methods combined selected 2,662 patients. There were 2,828 low-risk patients. Significant associations with hospital mortality were observed for: age, sites of admission, medical/unscheduled surgical admission, acute physiologic score of SAPS II, and the indicator variable “only Severity,” “only Intensity-of-care,” or MIX (developmental sample: calibration chi-square test, p = .205; area under the receiver operation characteristic curve, 0.814). Calibration and discrimination were better in our model than with the SAPS II model (unsplit sample). Conclusion:All three indicator variables select high-risk patients, the Severity/Intensity-of-care MIX being the most robust. These stratification criteria can improve case-mix selection for clinical and organizational studies.

Delirium: clinical approach and prevention.

Delirium, defined as an acute fluctuating change in mental state, with consciousness and cognitive impairment, has been found to have a high incidence in hospitalised patients, as well as being associated with increased morbidity and mortality, prolonged stays in the intensive care unit (ICU) and in hospital and higher costs. However, delirium is not easy to detect, since its diagnosis is mainly clinical. Yet the importance of early diagnosis and possible prevention in the different clinical scenarios is clear, to improve patient prognosis. This review provides a practical approach to delirium management through: (a) its classification and diagnosis utilising validated tools and (b) the use of non-pharmacological protocols and of an early prediction model to identify high-risk patients, who are more likely to benefit from pharmacological prophylaxis.

Conscious sedation in the critically ill ventilated patient

PURPOSE The aim of sedation is to provide comfort and minimize anxiety. However, adverse effects are noteworthy, and the optimal end point of sedation in intensive care unit patients is still debated. We analyzed if a level 2 on the Ramsay Scale (ie, awake, cooperative, oriented, tranquil patient) is suitable for an invasive therapeutic approach. MATERIALS AND METHODS Forty-two patients requiring respiratory support and sedation for at least 4 days were enrolled in a prospective interventional cohort study aiming at maintaining patients awake and collaborative. The Ramsay score was recorded 3 times a day. Once a day, the nurse in charge evaluated adequacy of sedation according to the compliance with nursing care and therapeutic maneuvers in the previous 24 hours. Data were collected until patients were ventilated. RESULTS Overall, 264 of 582 days were classified as conscious. Sedation was adequate in 93.9% of them. In conscious days, a higher Simplified Acute Physiology Score II score and male sex significantly correlated with inadequate sedation. CONCLUSIONS In a population of severe intensive care unit patients, conscious sedation was achieved in almost half of the days spent on ventilation. The positive implications (eg, on length of weaning and cost of sedation) of a conservative sedation strategy may be highly relevant.