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Featured researches published by Fanny P. Timm.


Annals of Surgery | 2016

Can sarcopenia quantified by ultrasound of the rectus femoris muscle predict adverse outcome of surgical intensive care unit patients as well as frailty? a prospective, observational cohort study

Noomi Mueller; Sushila Murthy; Christopher R. Tainter; Jarone Lee; Kathleen Riddell; Florian J. Fintelmann; Stephanie D. Grabitz; Fanny P. Timm; Benjamin Levi; Tobias Kurth; Matthias Eikermann

Objective: To compare sarcopenia and frailty for outcome prediction in surgical intensive care unit (SICU) patients. Background: Frailty has been associated with adverse outcomes and describes a status of muscle weakness and decreased physiological reserve leading to increased vulnerability to stressors. However, frailty assessment depends on patient cooperation. Sarcopenia can be quantified by ultrasound and the predictive value of sarcopenia at SICU admission for adverse outcome has not been defined. Methods: We conducted a prospective, observational study of SICU patients. Sarcopenia was diagnosed by ultrasound measurement of rectus femoris cross-sectional area. Frailty was diagnosed by the Frailty Index Questionnaire based on 50 variables. Relationship between variables and outcomes was assessed by multivariable regression analysis NCT02270502. Results: Sarcopenia and frailty were quantified in 102 patients and observed in 43.1% and 38.2%, respectively. Sarcopenia predicted adverse discharge disposition (discharge to nursing facility or in-hospital mortality, odds ratio 7.49; 95% confidence interval 1.47–38.24; P = 0.015) independent of important clinical covariates, as did frailty (odds ratio 8.01; 95% confidence interval 1.82–35.27; P = 0.006); predictive ability did not differ between sarcopenia and frailty prediction model, reflected by &khgr;2 values of 21.74 versus 23.44, respectively, and a net reclassification improvement (NRI) of −0.02 (P = 0.87). Sarcopenia and frailty predicted hospital length of stay and the frailty model had a moderately better predictive accuracy for this outcome. Conclusions: Bedside diagnosis of sarcopenia by ultrasound predicts adverse discharge disposition in SICU patients equally well as frailty. Sarcopenia assessed by ultrasound may be utilized as rapid beside modality for risk stratification of critically ill patients.


BMJ | 2017

Migraine and risk of perioperative ischemic stroke and hospital readmission: hospital based registry study

Fanny P. Timm; Timothy T. Houle; Stephanie D. Grabitz; Anne-Louise Lihn; Janne Bøgh Stokholm; Katharina Eikermann-Haerter; Ala Nozari; Tobias Kurth; Matthias Eikermann

Objective To evaluate whether patients with migraine are at increased risk of perioperative ischemic stroke and whether this may lead to an increased hospital readmission rate. Design Prospective hospital registry study. Setting Massachusetts General Hospital and two satellite campuses between January 2007 and August 2014. Participants 124 558 surgical patients (mean age 52.6 years; 54.5% women). Main outcome measures The primary outcome was perioperative ischemic stroke occurring within 30 days after surgery in patients with and without migraine and migraine aura. The secondary outcome was hospital readmission within 30 days of surgery. Exploratory outcomes included post-discharge stroke and strata of neuroanatomical stroke location. Results 10 179 (8.2%) patients had any migraine diagnosis, of whom 1278 (12.6%) had migraine with aura and 8901 (87.4%) had migraine without aura. 771 (0.6%) perioperative ischemic strokes occurred within 30 days of surgery. Patients with migraine were at increased risk of perioperative ischemic stroke (adjusted odds ratio 1.75, 95% confidence interval 1.39 to 2.21) compared with patients without migraine. The risk was higher in patients with migraine with aura (adjusted odds ratio 2.61, 1.59 to 4.29) than in those with migraine without aura (1.62, 1.26 to 2.09). The predicted absolute risk is 2.4 (2.1 to 2.8) perioperative ischemic strokes for every 1000 surgical patients. This increases to 4.3 (3.2 to 5.3) for every 1000 patients with any migraine diagnosis, 3.9 (2.9 to 5.0) for migraine without aura, and 6.3 (3.2 to 9.5) for migraine with aura.Patients with migraine had a higher rate of readmission to hospital within 30 days of discharge (adjusted odds ratio 1.31, 1.22 to 1.41). Conclusions Surgical patients with a history of migraine are at increased risk of perioperative ischemic stroke and have an increased 30 day hospital readmission rate. Migraine should be considered in the risk assessment for perioperative ischemic stroke.


Annals of Surgery | 2017

Effects of Intraoperative Fluid Management on Postoperative Outcomes: A Hospital Registry Study.

Christina H. Shin; D.R. Long; Duncan McLean; Stephanie D. Grabitz; Karim Ladha; Fanny P. Timm; Tharusan Thevathasan; Alberto Pieretti; Cristina R. Ferrone; Andreas Hoeft; Thomas Scheeren; B. T. Thompson; Tobias Kurth; Matthias Eikermann

Objective:Evaluate the dose-response relationship between intraoperative fluid administration and postoperative outcomes in a large cohort of surgical patients. Background:Healthy humans may live in a state of fluid responsiveness without the need for fluid supplementation. Goal-directed protocols driven by such measures are limited in their ability to define the optimal fluid state during surgery. Methods:This analysis of data on file included 92,094 adult patients undergoing noncardiac surgery with endotracheal intubation between 2007 and 2014 at an academic tertiary care hospital and two affiliated community hospitals. The primary exposure variable was total intraoperative volume of crystalloid and colloid administered. The primary outcome was 30-day survival. Secondary outcomes were respiratory complications within three postoperative days (pulmonary edema, reintubation, pneumonia, or respiratory failure) and acute kidney injury. Exploratory outcomes were postoperative length of stay and total cost of care. Our models were adjusted for patient-, procedure-, and anesthesia-related factors. Results:A U-shaped association was observed between the volume of fluid administered intraoperatively and 30-day mortality, costs, and postoperative length of stay. Liberal fluid volumes (highest quintile of fluid administration practice) were significantly associated with respiratory complications whereas both liberal and restrictive (lowest quintile) volumes were significantly associated with acute kidney injury. Moderately restrictive volumes (second quintile) were consistently associated with optimal postoperative outcomes and were characterized by volumes approximately 40% less than traditional textbook estimates: infusion rates of approximately 6–7 mL/kg/hr or 1 L of fluid for a 3-hour case. Conclusions:Intraoperative fluid dosing at the liberal and restrictive margins of observed practice is associated with increased morbidity, mortality, cost, and length of stay.


JAMA | 2018

Association of Preoperatively Diagnosed Patent Foramen Ovale With Perioperative Ischemic Stroke

Pauline Y. Ng; Andrew Y. Ng; Balachundhar Subramaniam; Sara M. Burns; Fanny Herisson; Fanny P. Timm; Cand Med; M. I. Rudolph; F.T. Scheffenbichler; Sabine Friedrich; Timothy T. Houle; Deepak L. Bhatt; Matthias Eikermann

Importance Perioperative stroke is a major complication for patients undergoing surgery. Patent foramen ovale (PFO) represents a possible anatomical link between venous thrombosis and stroke. Objective To determine whether a preoperatively diagnosed PFO is associated with increased risk of perioperative ischemic stroke. Design, Setting, and Participants Retrospective cohort study from Massachusetts General Hospital and 2 affiliated community hospitals between January 1, 2007, and December 31, 2015. Participants were 182 393 consecutive adults undergoing noncardiac surgery with general anesthesia. Exposures Preoperatively diagnosed PFO. Main Outcomes and Measures Perioperative ischemic stroke occurring within 30 days of surgery; stroke subtype by Oxfordshire Community Stroke Project classification and stroke severity by National Institute of Health Stroke Scale (NIHSS). Results Among the 150 198 patient cases analyzed (median [SD] age, 55 [16] years), 1540 (1.0%) had a diagnosis of PFO before surgery. A total of 850 (0.6%) ischemic strokes occurred within 30 days of surgery (49 [3.2%] among patients with PFO and 801 [0.5%] among patients without PFO). In adjusted analyses, patients with PFO had an increased risk of ischemic stroke compared with patients without PFO (odds ratio, 2.66 [95% CI, 1.96-3.63]; P < .001). The estimated risks of stroke were 5.9 for every 1000 patients with PFO and 2.2 for every 1000 patients without PFO (adjusted absolute risk difference, 0.4% [95% CI, 0.2%-0.6%). Patients with PFO also had an increased risk of large vessel territory stroke (relative risk ratio, 3.14 [95% CI, 2.21-4.48]; P < .001) and a more severe stroke-related neurologic deficit measured by NIHSS (median, 4 [interquartile range {IQR}, 2-10] vs median, 3 [IQR, 1-6] for those without PFO; P = .02). Conclusions and Relevance Among adult patients undergoing noncardiac surgery at 3 hospitals, having a preoperatively diagnosed PFO was significantly associated with increased risk of perioperative ischemic stroke within 30 days after surgery. Further research is needed to confirm these findings and to determine whether interventions would decrease this risk.


Anaesthesia | 2017

The association of postoperative pulmonary complications in 109,360 patients with pressure-controlled or volume-controlled ventilation.

Aranya Bagchi; M. I. Rudolph; Pauline Yeung Ng; Fanny P. Timm; D.R. Long; Shahzad Shaefi; Karim S. Ladha; M.F. Vidal Melo; Matthias Eikermann

We thought that the rate of postoperative pulmonary complications might be higher after pressure‐controlled ventilation than after volume‐controlled ventilation. We analysed peri‐operative data recorded for 109,360 adults, whose lungs were mechanically ventilated during surgery at three hospitals in Massachusetts, USA. We used multivariable regression and propensity score matching. Postoperative pulmonary complications were more common after pressure‐controlled ventilation, odds ratio (95%CI) 1.29 (1.21–1.37), p < 0.001. Tidal volumes and driving pressures were more varied with pressure‐controlled ventilation compared with volume‐controlled ventilation: mean (SD) variance from the median 1.61 (1.36) ml.kg−1 vs. 1.23 (1.11) ml.kg−1, p < 0.001; and 3.91 (3.47) cmH2O vs. 3.40 (2.69) cmH2O, p < 0.001. The odds ratio (95%CI) of pulmonary complications after pressure‐controlled ventilation compared with volume‐controlled ventilation at positive end‐expiratory pressures < 5 cmH2O was 1.40 (1.26–1.55) and 1.20 (1.11–1.31) when ≥ 5 cmH2O, both p < 0.001, a relative risk ratio of 1.17 (1.03–1.33), p = 0.023. The odds ratio (95%CI) of pulmonary complications after pressure‐controlled ventilation compared with volume‐controlled ventilation at driving pressures of < 19 cmH2O was 1.37 (1.27–1.48), p < 0.001, and 1.16 (1.04–1.30) when ≥ 19 cmH2O, p = 0.011, a relative risk ratio of 1.18 (1.07–1.30), p = 0.016. Our data support volume‐controlled ventilation during surgery, particularly for patients more likely to suffer postoperative pulmonary complications.


Critical Care Medicine | 2017

Dose-dependent Protective Effect of Inhalational Anesthetics Against Postoperative Respiratory Complications: A Prospective Analysis of Data on File From Three Hospitals in New England

Stephanie D. Grabitz; Hassan Farhan; Katarina J. Ruscic; Fanny P. Timm; Christina H. Shin; Tharusan Thevathasan; A.K. Staehr-Rye; Tobias Kurth; Matthias Eikermann

Objectives: Inhalational anesthetics are bronchodilators with immunomodulatory effects. We sought to determine the effect of inhalational anesthetic dose on risk of severe postoperative respiratory complications. Design: Prospective analysis of data on file in surgical cases between January 2007 and December 2015. Setting: Massachusetts General Hospital (tertiary referral center) and two affiliated community hospitals. Patients: A total of 124,497 adult patients (105,267 in the study cohort and 19,230 in the validation cohort) undergoing noncardiac surgical procedures and requiring general anesthesia with endotracheal intubation. Interventions: Median effective dose equivalent of inhalational anesthetics during surgery (derived from mean end-tidal inhalational anesthetic concentrations). Measurements and Main Results: Postoperative respiratory complications occurred in 6,979 of 124,497 cases (5.61%). High inhalational anesthetic dose of 1.20 (1.13–1.30) (median [interquartile range])-fold median effective dose equivalent versus 0.57 (0.45–0.64)-fold median effective dose equivalent was associated with lower odds of postoperative respiratory complications (odds ratio, 0.59; 95% CI, 0.53–0.65; p < 0.001). Additionally, high inhalational anesthetic dose was associated with lower 30-day mortality and lower cost. Inhalational anesthetic dose increase and reduced risk of postoperative respiratory complications remained significant in sensitivity analyses stratified by preoperative and intraoperative risk factors. Conclusions: Intraoperative use of higher inhalational anesthetic doses is strongly associated with lower odds of postoperative respiratory complications, lower 30-day mortality, and lower cost of hospital care. The authors speculate based on these data that sedation with inhalational anesthetics outside of the operating room may likewise have protective effects that decrease the risk of respiratory complications in vulnerable patients.


Anesthesiology | 2016

Effects of Depth of Propofol and Sevoflurane Anesthesia on Upper Airway Collapsibility, Respiratory Genioglossus Activation, and Breathing in Healthy Volunteers.

Jeroen C. P. Simons; Eric T. Pierce; Daniel Diaz-Gil; Sanjana A. Malviya; Matthew Meyer; Fanny P. Timm; Janne Bøgh Stokholm; Carl E. Rosow; Robert M. Kacmarek; Matthias Eikermann

Background:Volatile anesthetics and propofol impair upper airway stability and possibly respiratory upper airway dilator muscle activity. The magnitudes of these effects have not been compared at equivalent anesthetic doses. We hypothesized that upper airway closing pressure is less negative and genioglossus activity is lower during deep compared with shallow anesthesia. Methods:In a randomized controlled crossover study of 12 volunteers, anesthesia with propofol or sevoflurane was titrated using a pain stimulus to identify the threshold for suppression of motor response to electrical stimulation. Measurements included bispectral index, genioglossus electromyography, ventilation, hypopharyngeal pressure, upper airway closing pressure, and change in end-expiratory lung volume during mask pressure drops. Results:A total of 393 attempted breaths during occlusion maneuvers were analyzed. Upper airway closing pressure was significantly less negative at deep versus shallow anesthesia (−10.8 ± 4.5 vs. −11.3 ± 4.4 cm H2O, respectively [mean ± SD]) and correlated with the bispectral index (P < 0.001), indicating a more collapsible airway at deep anesthesia. Respiratory genioglossus activity during airway occlusion was significantly lower at deep compared with light anesthesia (26 ± 21 vs. 35 ± 24% of maximal genioglossus activation, respectively; P < 0.001) and correlated with bispectral index (P < 0.001). Upper airway closing pressure and genioglossus activity during airway occlusion did not differ between sevoflurane and propofol anesthesia. Conclusions:Propofol and sevoflurane anesthesia increased upper airway collapsibility in a dose-dependent fashion with no difference at equivalent anesthetic concentrations. These effects can in part be explained by a dose-dependent inhibiting effect of anesthetics on respiratory genioglossus activity.


Sleep | 2018

Effects of Opioids Given to Facilitate Mechanical Ventilation on Sleep Apnea After Extubation in the Intensive Care Unit

Fanny P. Timm; Sebastian Zaremba; Stephanie D. Grabitz; Hassan Farhan; Stefanie Zaremba; Elizabeth Siliski; Christina H. Shin; Sandra Muse; Sabine Friedrich; James Mojica; Tobias Kurth; Matthias Eikermann

Study Objectives Following extubation in the intensive care unit (ICU), upper airway (UA) edema and respiratory depressants may promote UA dysfunction. We tested the hypothesis that opioids increase the risk of sleep apnea early after extubation. Methods Fifty-six ICU patients underwent polysomnography the night after extubation. Airflow limitation during wakefulness was identified using bedside spirometry. Correlation and ordinal regression analyses were used to quantify the effects of preextubation opioid dose on postextubation apnea-hypopnea index (AHI) and severity of sleep apnea and whether or not inspiratory airway obstruction (ratio of maximum expiratory and inspiratory airflows at 50% of vital capacity [MEF50/MIF50] ≥ 1) during wakefulness predicts airway obstruction during sleep. Data were adjusted for age, gender, body mass index, as well as a generalized propensity score balanced for APACHE II, score for preoperative prediction of obstructive sleep apnea, duration of mechanical ventilation, chronic obstructive pulmonary disease, and a procedural severity score for morbidity. Results Sleep apnea (AHI ≥ 5) was present in 40 (71%) of the 56 patients. Morphine equivalent dose given 24 hours prior extubation predicted obstructive respiratory events during sleep (r = 0.35, p = .01) and sleep apnea (odds ratio [OR] 1.17; 95% confidence interval [CI] 1.02-1.34). Signs of inspiratory UA obstruction (MEF50/MIF50 ≥ 1) assessed by bedside spirometry were strongly associated with sleep apnea (OR 5.93; 95% CI 1.16-30.33). Conclusions High opioid dose given 24 hours prior to extubation increases the likelihood of postextubation sleep apnea in the ICU, particularly in patients with anatomical vulnerability following extubation.


Anaesthesia | 2018

Implementation of a new strategy to improve the peri-operative management of neuromuscular blockade and its effects on postoperative pulmonary complications

M. I. Rudolph; Hovig V. Chitilian; Pauline Yeung Ng; Fanny P. Timm; Aalok V. Agarwala; A. B. Doney; Timothy T. Houle; Matthias Eikermann

Inappropriate dosing of neostigmine for antagonism of neuromuscular blockade has been associated with postoperative pulmonary complications. We evaluated the effects of a quality improvement initiative tailored to optimise the use of neostigmine in antagonising neuromuscular blockade on postoperative pulmonary complications, costs and duration of hospital stay. The quality improvement initiative consisted of: a reduction in available neostigmine aliquot sizes; a cognitive aid; an educational component; and a financial incentive for the intra‐operative documentation of train‐of‐four measurement before administration of neostigmine. We conducted a pre‐specified analysis of data obtained in our quality improvement study. Additional analyses were conducted in a propensity‐matched cohort. An interrupted time series design was used to discriminate between the intervention and a counterfactual scenario. We analysed 12,025 consecutive surgical cases performed in 2015. Postoperative pulmonary complications occurred in 220 (7.5%) of 2937 cases pre‐intervention and 568 (6.3%) of 9088 cases post‐intervention. Adjusted regression analyses showed significantly a lower risk of postoperative pulmonary complications (OR 0.73 (95%CI 0.61–0.88); p = 0.001), lower costs (incidence rate ratio 0.95 (95%CI 0.93–0.97); p < 0.001) and shorter duration of hospital stay (incidence rate ratio 0.91 (95%CI 0.87–0.94); p < 0.001) after implementation of the quality improvement initiative. Analyses in a propensity‐matched sample (n = 2936 per group) and interrupted time series analysis (n = 27,202 cases) confirmed the findings. Our data show that a local, multifaceted quality improvement initiative can enhance the quality of intra‐operative neuromuscular blocking agent utilisation, thereby reducing the incidence of postoperative pulmonary complications.


BMC Anesthesiology | 2017

Development and validation of a Score for Preoperative Prediction of Obstructive Sleep Apnea (SPOSA) and its perioperative outcomes

Christina H. Shin; Stephanie D. Grabitz; Fanny P. Timm; Noomi Mueller; Khushi Chhangani; Karim S. Ladha; Scott Devine; Tobias Kurth; Matthias Eikermann

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