About Pat Neligan

Pat Neligan lives and works in Galway, Ireland

2023 Western Anaesthesia Symposium: Knockranny House Hotel, March 24th and 25th 2023


Tickets Here

Friday March 24th 2023

14.00 – 15.00 Session 1 Clinical Forum

(Including the Best papers of 2022-23)

Prof. Patrick Neligan, Galway

Dr Sinead Bredin, Sligo

Dr Martina Melvin, Galway

Dr Mark Ross, Galway

15.00-15.30 Coffee Break

15.30 – 16.30 Session 2

Anesthesiology Review 1- Forgotten Issues in Airway Management and Care

Three Cases – Curious Airways – Dr Michael Callaghan, Galway

Dr Craig Lyons, London

Post Operative Sore Throat – Dr Colm Keane, Mayo

17.00 – 18.00 Session 3

Anaesthesiology Review 2 – Stuff We Give to Our Patients – Does it Harm or Heal?

PONV Prophylaxis – useful or a mindless ritual? Dr Leo Kevin, Galway

Drugs we add to Local Anaesthetics – do they work? Dr Brian Kinirons, Galway

Intravenous Clonidine in Perioperative Medicine – does it work? Is it safe? Prof. Michelle Duggan, Mayo

18.15 – 19.00 Session 4 Snap Talks

The Current State of Research in Anaesthesiology & Critical Care

“(what if) I (had) stopped reading journals in June 2000; did I miss anything?” Prof. Pat Neligan

Clinical Research and Where it is Heading – Prof. John Laffey

Basic Science Research and Where it is Heading – Prof. Max Kelz

19.15 – 20.00 Session 5

Guest Lecture

Ciaran Carthy – “Aviation: Turns Out We’re Not as Safe as We Thought”

20.30 DINNER (Buffet- Included in Registration)

Saturday March 25th 2023

8.00 – 09.00 Session 1 Case Reports – O’Beirne-Costello Medal

Chaired by Dr Michael Scully

9.15 – 10.45 Session 2: University of Galway Session

Prof. Felicity Platt (Queen Charlotte’s & Hammersmith Hospitals in London)– “Medico-Legal Pitfalls in Obstetric Anaesthesia”

Prof. Max Kelz (University of Pennsylvania, USA)- “Sex Drugs and Rock and Roll Anesthetic Sensitivity: Female Brains Exhibit Higher Propensity to the Waking State”

10.45 – 11.10

Coffee Break

11.10 – 12.40 Session 3: Patient Safety & Medical Education

Ciaran Carthy – “Decision Making -A Core Competence for Anaesthesiologists & Pilots “

Prof. Rachel Rapaport Kelz (Professor of Surgery, University of Pennsylvania, USA) – “Deliberate Medical Education”

12.40 – 13.30 Session 4 Plenary Lecture

John Carlisle (Torbay Hospital, UK)- “Uncovering Academic Fraud”

Lunch (Included in Registration)

14.30 – 16.30 Session 5 Critical Care Anesthesiology

Prof John Bates (Galway), Dr. David Cosgrave (Galway), Dr Peter Moran (Galway), Dr Sinead Egan (Mayo)

A 70 year old male presents for laparotomy consequent of a perforated diverticulum

1. The patient has a plasma sodium of 109mmol/l

2. The patient has a serum creatinine of 400mmol/L (it was normal 2 weeks previously)

3. The patient has plasma ketones of 6mmol/l

The patient has all three.

The 2022 Symposium Is ON – In Person

We are delighted to announce that the 41st Western Anaesthesiology & Critical Care Symposium (WAS) is on – in person – at Glenlo Abbey Hotel, Galway, on March 25th and 26th. Because of the short timescale for organising the meeting, the meeting will feature mostly local talent – all of your controversial favorites plus some new exciting speakers. It will be a great opportunity to learn something new and catch up with a few (dozen) old friends.

Full details are HERE.

SOLAR trial – Saline vs Lactated Ringers’

solar trialThe SOLAR trial, which compared a composite outcomes in perioperative colorectal or orthopaedic patients, assigned to Lactated Ringers’ (similar to Hartmann’s) solution – over 2 week blocks over a few years (8,616), has been published this month in Anesthesiology. The median volume of fluid administered in the perioperative period was 1.9L, and, no surprise here – there was no difference in outcomes.

Here is the blurb from the abstract:

“Among 8,616 qualifying patients, 4,187 (49%) were assigned to lactated Ringer’s solution, and 4,429 (51%) were assigned to saline. Each group received a median 1.9 l of fluid. The primary composite of major complications was observed in 5.8% of lactated Ringer’s versus 6.1% of normal saline patients, with estimated average relative risk across the components of the composite of 1.16 (95% CI, 0.89 to 1.52; P = 0.261). The secondary outcome, postoperative acute kidney injury, Acute Kidney Injury Network stage I–III versus 0, occurred in 6.6% of lactated Ringer’s patients versus 6.2% of normal saline patients, with an estimated relative risk of 1.18 (99.3% CI, 0.99 to 1.41; P = 0.009, significance criterion of 0.007). Absolute differences between the treatment groups for each outcome were less than 0.5%, an amount that is not clinically meaningful.”

The two litres of Saline / LR did not cause acidosis or meaningful increase in plasma chloride concentrations at 24 hours – chloride rose in both groups initially and then fell off. If the median volume of fluid was 2L – then there was a median difference in chloride intake of 80mmol – roughly what is in half a litre of saline. There is good reason to believe that hyperchloraemic fluids (such as LR and Saline) in lowish volume (2L) don’t change acid base status, due to dilution of albumin and then clearance.  It would have been really helpful to know what, if any, iv fluid was given post op and how much sodium and chloride the patients received over the 3 days of the stress response.

These results differ from the SMART-MED and SALT-ED trials – which despite extraordinarily small volumes of fluid, purported to show an increase in complications – particularly renal with saline. Presumably, critically ill and emergency room patients are at greater risk for organ dysfunction, and the additional sodium and chloride pushed a few “over the edge.”

An impressive study that shows that any anaesthesia department can do important research just by altering one component of “what we always do” every couple of weeks and then looking at outcomes from a largish cohort. It won’t change my practice, and I would dearly have liked to see the study done with plasmalyte-148 rather than LR.

Nitrous SAVES lives? Maybe, but the discussion is still open….

Following Paul Myles’ paper in Anesthesiology in 2007 – that demonstrated bad outcomes in patients anaesthetised with nitrous oxide (click here), “experts” clamoured to demand that we stop using the stuff in our clinical practice. Their opinions were enhanced by the ENIGMA trial, that claimed increased risk of myocardial infarction in patients receiving nitrous (click here); following adjustment for the usual factors.  I have been personally accused of “poisoning” my patients by continuing to administer nitrous. Hence, it was with great relief that I read this paper (click here) in this month’s anesthesia and analgesia.
Turan and Colleagues evaluated almost 50,000 patients who had noncardiac surgery at the Cleveland Clinic over a 4 year period (2005 and 2009). Of the patients that had general anesthesia, 17,00 were given N2O (45%) and 21,000 were not (55%). Of each group, 10,000 patients were propensity score-matched  on 30-day mortality and a set of 8 in-hospital morbidity/mortality outcomes.
The results were surprising. Patients that were given N2O intraoperatively had decreased odds of 30-day mortality (odds ratio [OR]: 97.5% confidence interval, 0.67, 0.46–0.97; P= 0.02), compared with no nitrous. In addition, patients that received  had a17% (OR: 0.83, 0.74–0.92) reduced odds of experiencing major in-hospital morbidity/mortality than non-nitrous (P < 0.001). In particular, the risk of pulmonary complications with significantly lower in patients who received nitrous.(OR, 95% Bonferroni-adjusted CI: 0.59, 0.44–0.78).
Ok – so this was a propensity score analysis induced fluke – right? In the same issue of A&A we have a second paper that analysed the POISE trial outcomes (click here). 30% of the 6000 patients in the study received nitrous – and there was NO association between the gas and adverse outcomes. A fairly biased editorial in A&A, written with the help of Paul Myles, whose group is the only one that has demonstrated bad outcomes with nitrous, dismembers the Turan paper.
Nitrous oxide has been around for 160 years. I am not aware that there is a pandemic of death and MI amongst the patients of those of us who use the stuff. In any case, I think that this paper, at the very least, suggests that the jury is still out on the subject.

Surviving Sepsis Guidelines 2013

The most recent iteration of Surviving Sepsis has been published in Critical Care Medicine and Intensive Care Medicine. The can be downloaded here (please click).

Below is a summary of the Guidelines:

A. Initial Resuscitation

1. Protocolized, quantitative resuscitation of patients with sepsis-induced tissue hypoperfusion (defined in this document as hypotension persisting after initial fluid challenge or blood lactate concentration ≥ 4 mmol/L).

Goals during the first 6 hrs of resuscitation:

a) Central venous pressure 8–12 mm Hg

b) Mean arterial pressure (MAP) ≥ 65 mm Hg c) Urine output ≥ 0.5 mL/kg/hr d) Central venous (superior vena cava) or mixed venous oxygen saturation 70% or 65%, respectively (grade 1C).

c). In patients with elevated lactate levels targeting resuscitation to normalize lactate (grade 2C).

B. Screening for Sepsis and Performance Improvement

1. Routine screening of potentially infected seriously ill patients for severe sepsis to allow earlier implementation of therapy (grade 1C).

2. Hospital–based performance improvement efforts in severe sepsis (UG).

 C. Diagnosis

1. Cultures as clinically appropriate before antimicrobial therapy if no significant delay (> 45 mins) in the start of antimicrobial(s) (grade 1C). At least 2 sets of blood cultures (both aerobic and anaerobic bottles) be obtained before antimicrobial therapy with at least 1 drawn percutaneously and 1 drawn through each vascular access device, unless the device was recently (<48 hrs) inserted (grade 1C).

2. Use of the 1,3 beta-D-glucan assay (grade 2B), mannan and anti-mannan antibody assays (2C), if available, and invasive candidiasis is in differential diagnosis of cause of infection.

3. Imaging studies performed promptly to confirm a potential source of infection (UG).

D. Antimicrobial Therapy

1. Administration of effective intravenous antimicrobials within the first hour of recognition of septic shock (grade 1B) and severe sepsis without septic shock (grade 1C) as the goal of therapy.

2a. Initial empiric anti-infective therapy of one or more drugs that have activity against all likely pathogens (bacterial and/or fungal or viral) and that penetrate in adequate concentrations into tissues presumed to be the source of sepsis (grade 1B).

2b. Antimicrobial regimen should be reassessed daily for potential de-escalation (grade 1B).

3. Use of low procalcitonin levels or similar biomarkers (e.g. CRP) to assist the clinician in the discontinuation of empiric antibiotics in patients who initially appeared septic, but have no subsequent evidence of infection (grade 2C).

4a. Combination empirical therapy for neutropenic patients with severe sepsis (grade 2B) and for patients with difficult-to-treat, multidrug-resistant bacterial pathogens such as Acinetobacter and Pseudomonas spp. (grade 2B). For patients with severe infections

associated with respiratory failure and septic shock, combination therapy with an extended spectrum beta-lactam and either an aminoglycoside or a fluoroquinolone is for P. aeruginosa bacteremia (grade 2B). A combination of beta-lactam and macrolide for

patients with septic shock from bacteremic Streptococcus pneumoniae infections (grade 2B).

4b. Empiric combination therapy should not be administered for more than 3–5 days. De-escalation to the most appropriate single therapy should be performed as soon as the susceptibility profile is known (grade 2B).

5. Duration of therapy typically 7–10 days; longer courses may be appropriate in patients who have a slow clinical response, undrainable foci of infection, bacteremia with S. aureus; some fungal and viral infections or immunologic deficiencies, including neutropenia (grade 2C).

6. Antiviral therapy initiated as early as possible in patients with severe sepsis or septic shock of viral origin (grade 2C).

7. Antimicrobial agents should not be used in patients with severe inflammatory states determined to be of noninfectious cause (UG).

E. Source Control

1. A specific anatomical diagnosis of infection requiring consideration for emergent source control be sought and diagnosed or excluded as rapidly as possible, and intervention be undertaken for source control within the first 12 hr after the diagnosis is made, if feasible (grade 1C).

2. When infected peripancreatic necrosis is identified as a potential source of infection, definitive intervention is best delayed until adequate demarcation of viable and nonviable tissues has occurred (grade 2B).

3. When source control in a severely septic patient is required, the effective intervention associated with the least physiologic insult should be used (eg, percutaneous rather than surgical drainage of an abscess) (UG).

4. If intravascular access devices are a possible source of severe sepsis or septic shock, they should be removed promptly after other vascular access has been established (UG).

F. Infection Prevention

1a. Selective oral decontamination and selective digestive decontamination should be introduced and investigated as a method to reduce the incidence of ventilator-associated pneumonia; this infection control measure can then be instituted in health care settings and regions where this methodology is found to be effective (grade 2B).

1b. Oral chlorhexidine gluconate be used as a form of oropharyngeal decontamination to reduce the risk of ventilator-associated pneumonia in ICU patients with severe sepsis (grade 2B).

G. Fluid Therapy of Severe Sepsis

1. Crystalloids as the initial fluid of choice in the resuscitation of severe sepsis and septic shock (grade 1B).

2. Against the use of hydroxyethyl starches for fluid resuscitation of severe sepsis and septic shock (grade 1B).

3. Albumin in the fluid resuscitation of severe sepsis and septic shock when patients require substantial amounts of crystalloids (grade 2C).

4. Initial fluid challenge in patients with sepsis-induced tissue hypoperfusion with suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (a portion of this may be albumin equivalent). More rapid administration and greater amounts of fluid may be needed in some patients (grade 1C).

5. Fluid challenge technique be applied wherein fluid administration is continued as long as there is hemodynamic improvement either based on dynamic (eg, change in pulse pressure, stroke volume variation) or static (eg, arterial pressure, heart rate) variables (UG).

H. Vasopressors

1. Vasopressor therapy initially to target a mean arterial pressure (MAP) of 65 mm Hg (grade 1C).

2. Norepinephrine as the first choice vasopressor (grade 1B).

3. Epinephrine (added to and potentially substituted for norepinephrine) when an additional agent is needed to maintain adequate blood pressure (grade 2B).

4. Vasopressin 0.03 units/minute can be added to norepinephrine (NE) with intent of either raising MAP or decreasing NE dosage (UG).

5. Low dose vasopressin is not recommended as the single initial vasopressor for treatment of sepsis-induced hypotension and vasopressin doses higher than 0.03-0.04 units/minute should be reserved for salvage therapy (failure to achieve adequate MAP with other vasopressor agents) (UG).

6. Dopamine as an alternative vasopressor agent to norepinephrine only in highly selected patients (eg, patients with low risk of tachyarrhythmias and absolute or relative bradycardia) (grade 2C).

7. Phenylephrine is not recommended in the treatment of septic shock except in circumstances where (a) norepinephrine is associated with serious arrhythmias,

(b) cardiac output is known to be high and blood pressure persistently low or (c) as salvage therapy when combined inotrope/vasopressor drugs and low dose vasopressin have failed to achieve MAP target (grade 1C).

8. Low-dose dopamine should not be used for renal protection (grade 1A).

9. All patients requiring vasopressors have an arterial catheter placed as soon as practical if resources are available (UG).

I. Inotropic Therapy

1. A trial of dobutamine infusion up to 20 micrograms/kg/min be administered or added to vasopressor (if in use) in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of

hypoperfusion, despite achieving adequate intravascular volume and adequate MAP (grade 1C).

2. Not using a strategy to increase cardiac index to predetermined supranormal levels (grade 1B).

J. Corticosteroids

1. Not using intravenous hydrocortisone to treat adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (see goals for Initial Resuscitation). In case this is not achievable, we suggest intravenous hydrocortisone alone at a dose of 200 mg per day (grade 2C).

2. Not using the ACTH stimulation test to identify adults with septic shock who should receive hydrocortisone (grade 2B).

3. In treated patients hydrocortisone tapered when vasopressors are no longer required (grade 2D).

4. Corticosteroids not be administered for the treatment of sepsis in the absence of shock (grade 1D).

5. When hydrocortisone is given, use continuous flow (grade 2D).

K. Blood Product Administration

1. Once tissue hypoperfusion has resolved and in the absence of extenuating circumstances, such as myocardial ischemia, severe hypoxemia, acute hemorrhage, or ischemic heart disease, we recommend that red blood cell transfusion occur only when hemoglobin concentration decreases to <7.0 g/dL to target a hemoglobin concentration of 7.0 –9.0 g/dL in adults (grade 1B).

2. Not using erythropoietin as a specific treatment of anemia associated with severe sepsis (grade 1B).

3. Fresh frozen plasma not be used to correct laboratory clotting abnormalities in the absence of bleeding or planned invasive procedures (grade 2D).

4. Not using antithrombin for the treatment of severe sepsis and septic shock (grade 1B).

5. In patients with severe sepsis, administer platelets prophylactically when counts are <10,000/mm3 (10 x 109/L) in the absence of apparent bleeding. We suggest prophylactic platelet transfusion when counts are < 20,000/mm3 (20 x 109/L) if the patient has a significant risk of bleeding. Higher platelet counts (≥50,000/mm3 [50 x 109/L]) are advised for active bleeding, surgery, or invasive procedures (grade 2D).

L. Immunoglobulins

1. Not using intravenous immunoglobulins in adult patients with severe sepsis or septic shock (grade 2B).

M. Selenium

1. Not using intravenous selenium for the treatment of severe sepsis (grade 2C).

N. History of Recommendations Regarding Use of rhAPC

A history of the evolution of SSC recommendations as to rhAPC (no longer available) is provided.

O. Mechanical Ventilation of Sepsis-Induced ARDS

1. Target a tidal volume of 6 mL/kg predicted body weight in patients with sepsis-induced ARDS (grade 1A vs. 12 mL/kg).

2. Plateau pressures be measured in patients with ARDS and initial upper limit goal for plateau pressures in a passively inflated lung be ≤30 cm H2O (grade 1B).

3. Positive end-expiratory pressure (PEEP) be applied to avoid alveolar collapse at end expiration (atelectotrauma) (grade 1B).

4. Strategies based on higher rather than lower levels of PEEP be used for patients with sepsis-induced moderate or severe ARDS (grade 2C).

5. Recruitment maneuvers be used in sepsis patients with severe refractory hypoxemia (grade 2C).

6. Prone positioning be used in sepsis-induced ARDS patients with a Pao2/Fio2 ratio ≤100 mm Hg in facilities that have experience with such practices (grade 2B).

7. That mechanically ventilated sepsis patients be maintained with the head of the bed elevated to 30-45 degrees to limit aspiration risk and to prevent the development of ventilator-associated pneumonia (grade 1B).

8. That noninvasive mask ventilation (NIV) be used in that minority of sepsis-induced ARDS patients in whom the benefits of NIV have been carefully considered and are thought to outweigh the risks (grade 2B).

9. That a weaning protocol be in place and that mechanically ventilated patients with severe sepsis undergo spontaneous breathing trials regularly to evaluate the ability to discontinue mechanical ventilation when they satisfy the following criteria:

a) arousable; b) hemodynamically stable (without vasopressor agents); c) no new potentially serious conditions; d) low ventilatory and end-expiratory pressure requirements; and e) low Fio2 requirements which can be met safely delivered with a face mask or nasal cannula. If the spontaneous breathing trial is successful, consideration should be given for extubation (grade 1A).

10. Against the routine use of the pulmonary artery catheter for patients with sepsis induced ARDS (grade 1A).

11. A conservative rather than liberal fluid strategy for patients with established sepsis-induced ARDS who do not have evidence of tissue hypoperfusion (grade 1C).

12. In the absence of specific indications such as bronchospasm, not using beta 2-agonists for treatment of sepsis-induced ARDS (grade 1B).

P. Sedation, Analgesia, and Neuromuscular Blockade in Sepsis

1. Continuous or intermittent sedation be minimized in mechanically ventilated sepsis patients, targeting specific titration endpoints (grade 1B).

2. Neuromuscular blocking agents (NMBAs) be avoided if possible in the septic patient without ARDS due to the risk of prolonged neuromuscular blockade following discontinuation. If NMBAs must be maintained, either intermittent bolus as

required or continuous infusion with train-of-four monitoring of the depth of blockade should be used (grade 1C). 3. A short course of NMBA of not greater than 48 hours for patients with early sepsis-induced ARDS and a Pao2/Fio2 < 150 mm Hg (grade 2C).

Q. Glucose Control

1. A protocolized approach to blood glucose management in ICU patients with severe sepsis commencing insulin dosing when 2 consecutive blood glucose levels are >180 mg/dL. This protocolized approach should target an upper blood glucose ≤180 mg/dL rather than an upper target blood glucose ≤ 110 mg/dL (grade 1A).

2. Blood glucose values be monitored every 1–2 hrs until glucose values and insulin infusion rates are stable and then every 4 hrs thereafter (grade 1C).

3. Glucose levels obtained with point-of-care testing of capillary blood be interpreted with caution, as such measurements may not accurately estimate arterial blood or plasma glucose values (UG).

R. Renal Replacement Therapy

1. Continuous renal replacement therapies and intermittent hemodialysis are equivalent in patients with severe sepsis and acute renal failure (grade 2B).

2. Use continuous therapies to facilitate management of fluid balance in hemodynamically unstable septic patients (grade 2D).

S. Sodium Bicarbonate Therapy

1. Not using sodium bicarbonate therapy for the purpose of improving hemodynamics or reducing vasopressor requirements in patients with hypoperfusion-induced lactic acidemia with pH ≥7.15 (grade 2B).

T. Deep Vein Thrombosis Prophylaxis

1. Patients with severe sepsis receive daily pharmacoprophylaxis against venous thromboembolism (VTE) (grade 1B). This should be accomplished with daily subcutaneous low-molecular weight heparin (LMWH) (grade 1B versus twice daily UFH, grade 2C versus three times daily UFH). If creatinine clearance is <30 mL/min, use dalteparin (grade 1A) or another form of LMWH that has a low degree of renal metabolism (grade 2C) or UFH (grade 1A).

2. Patients with severe sepsis be treated with a combination of pharmacologic therapy and intermittent pneumatic compression devices whenever possible (grade 2C).

3. Septic patients who have a contraindication for heparin use (eg, thrombocytopenia, severe coagulopathy, active bleeding, recent intracerebral hemorrhage) not receive pharmacoprophylaxis (grade 1B), but receive mechanical prophylactic treatment, such

as graduated compression stockings or intermittent compression devices (grade 2C), unless contraindicated. When the risk decreases start pharmacoprophylaxis (grade 2C).

U. Stress Ulcer Prophylaxis

1. Stress ulcer prophylaxis using H2 blocker or proton pump inhibitor be given to patients with severe sepsis/septic shock who have bleeding risk factors (grade 1B).

2. When stress ulcer prophylaxis is used, proton pump inhibitors rather than H2RA (grade 2D)

3. Patients without risk factors do not receive prophylaxis (grade 2B).

V. Nutrition

1. Administer oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 hours after a diagnosis of severe sepsis/septic shock (grade 2C).

2. Avoid mandatory full caloric feeding in the first week but rather suggest low dose feeding (eg, up to 500 calories per day), advancing only as tolerated (grade 2B).

3. Use intravenous glucose and enteral nutrition rather than total parenteral nutrition (TPN) alone or parenteral nutrition in conjunction with enteral feeding in the first 7 days after a diagnosis of severe sepsis/septic shock (grade 2B).

4. Use nutrition with no specific immunomodulating supplementation rather than nutrition providing specific immunomodulating supplementation in patients with severe sepsis (grade 2C).

W. Setting Goals of Care

1. Discuss goals of care and prognosis with patients and families (grade 1B).

2. Incorporate goals of care into treatment and end-of-life care planning, utilizing palliative care principles where appropriate (grade 1B).

3. Address goals of care as early as feasible, but no later than within 72 hours of ICU admission (grade 2C).

Source: Dellinger RP, Levy MM, Rhodes A, et al: Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013; 41:580-637

Taking slow vent weans by the collar

Our ICUs are crowded by patients that are slow to liberate from mechanical ventilation. In North America, such patients are often transferred to long term mechanical ventilation facilities (LTAC) – where they are weaned to liberation. There are many strategies for weaning tracheostomised  patients from mechanical ventilation – a progressive reduction in pressure support, intermittent tracheal mask (trach collar) trials, external CPAP etc.

Martin Tobin has, for many years, questioned the now conventional wisdom of progressive pressure support weans, and in this weeks JAMA his group have published a paper comparing Volume Assist Control Ventilation with intermittent tracheal mask trials to progressive pressure support weaning. The patients in the pressure support group (PSG) started, if they were able to tolerate it, pressure support ventilation at 14cmH2O. Tolerance to wean was checked every 6 hours, and 2cmH2O decrements of PS were applied up to a maximum of 6cmH2O per day. Once the pressure support reached 6cmH2O, a 5 day vent liberation process began. In the tracheal mask group (TMG), patients were put on tracheal mask  for up to 12 hours per day for 2 days (then back on assist control) and on day 3 started on the 5 day vent liberation programme.

The primary outcome was weaning duration, defined from the first day of randomization to the day the patient was successfully weaned. Weaning was considered successful when patients breathed without ventilator assistance for at least 5 days. If the patients had not liberated by day 45, this was considered “failure to wean.”

Three hundred and twelve patients were randomized, of which one third died while in the study (equal numbers each group). Among the entire group of randomized patients (n = 312), median weaning time was shorter in TMG versus PSG: 15 days (IQR, 8-25) vs 19 days (IQR, 12-31), P = .004.. Among patients who completed the study (n = 194), median weaning time was shorter in TMG vs PSG: 13 days (IQR, 8-30) vs 19 days (12-43), P = .006.

Weaning time had no effect on survival at 6 and 12 months.

Impression: this article suggests that weaning patients using decrements of pressure support is not aggressive enough and that weaning in more likely to be successful with unassisted tracheal mask. Although, unsurprisingly, this had no effect on survival, a 6 day reduction in ventilator times translates into considerable resource savings – particularly with ICU/HDU beds are very scarce (as in our hospitals). Whether or not patients should be weaned from assist-control or high levels of pressure support appear moot: I doubt that it makes a difference. I continue to see any value for using external CPAP through a t-piece as a vent liberation process: there is not a shred of supportive evidence.

High Frequency Oscillation – Shaken by Bad News!

oscillatorSummary: Two Papers Published Online in the NEJM, OSCILLATE and OSCAR, have failed to demonstrate that HFOV benefits patients with ARDS. In the OSCILLATE study there was an 11% increase in 28 day mortality (NNH 9). HFOV should not be used in routine management of patients with ARDS.

For the past two decades many intensivists have used an “open lung” approach to managing hypoxaemia in ARDS. This approach involves using high levels of PEEP, inverse ratio ventilation (IRV), airway pressure release ventilation (APRV) or high frequency oscillation ventilation (HFOV) – to keep severely injured lungs in a state of inflation during most of the respiratory cycle. “Open Lung” can be achieved by using high PEEP and small tidal volumes, or moderate levels of PEEP and long inspiratory times. In either case mean airway pressure increases. The most sophisticated method of using PEEP involves the construction of pressure volume curves and setting the PEEP above the lower inflection point. To date, the high PEEP approach has neither been proven to be better or worse than the incremental PEEP approach based on fiO2. However a 2010 meta-analysis has suggested that high PEEP may be beneficial in ARDS. With long inspiratory times oxygenation occurs principally during inspiration rather than expiration; functionally ventilation occurs on the expiratory limb of the volume-pressure curve.
There is good physiologic reasoning behind the open lung approach. Severe ARDs is characterized by massive atelectasis, increased lung water and pleural effusions; functional residual capacity is obliterated. As most gas exchange occurs in expiration, and end expiratory lung volumes are lost, open lung approaches use the inspiratory reserve volume. Further, it is widely believed that phasic opening and closing of injured lung units and uninjured adjacent units results in ventilator induced lung injury (atelectrauma). Open lung approaches prevent atelectrauma. The majority of ICUs utilize conventional ventilator strategies such as pressure support, pressure control (or bilevel) or volume assist-control in early ARDs. However, in patients with severe and refractory hypoxic respiratory failure, units differ between using high PEEP and so called “advanced” modes to maintain oxygenation. Despite the conceptual attractiveness of IRV, APRV and HFOV there has always been an evidence gap in support of these modes: nobody knows how much the lung stretches. There is no easy way to measure end inspiratory lung volumes and hence to evaluate the risk of volutrauma. Proponents of “advanced” modes will argue that absence of evidence does not mean absence of efficacy: clearly open lung modes of ventilation improve oxygenation – so this must be good. However, we have decades of data suggesting that prone positioning improves oxygenation, but not outcomes.

After a long wait, we have now seen the publication of two studies on HFOV – the multi-national OSCILLATE study, and UK based OSCAR trial. The results are not good.


Background and Methods: This was a multi center trial of 38 hospitals in Canada, the United States, Saudi Arabia, Chile, and India from July 2009 thru August 2012. Patients were eligible for inclusion if they had had an onset of pulmonary symptoms within the previous 2 weeks (i.e. this was an acute illness), had been intubated, had hypoxemia defined as a PaO2/FiO2 (PF) ratio of ≤200, with an FiO2 of ≥0.5), and had bilateral infiltrates on CXR. These criteria must have been met within the previous 72 hours. The authors were careful – patients who met criteria were put on pressure control ventilation, TV 600ml, FiO2 0.6 and PEEP 10cmH2O. If, after 30 minutes, the PF ratio was still below 200, the patients were enrolled in the trial. Patients were randomized to HFOV or conventional ventilation (CV). The patients were remarkably well balanced at baseline – and very sick – with mean Apache II scores in both groups of 29.

Technique: a recruitment maneuver was performed initially (40cmH2O for 40 seconds) then HFOV was commenced at a mean airway pressure of 30 cmH2O, adjusted to keep the PaO2 between 55 to 80 mm Hg (7.3 to 10.5 kPa). The frequency was adjusted to keep the pH above 7.2. Once mean airway pressure (mPaw) dipped below 24 cmH2O conversion to CV was considered; if mPaw went below 20cmH2O – conversion was mandatory. The CV group received a recruitment maneuver, then pressure controlled ventilation with TV 6ml/Kg and PEEP adjusted according to protocol. Initial PEEP was 20cmH2O. Patients could also receive volume assist control or pressure support ventilation. For patients with good compliance and gas exchange (presumably during the weaning phase), the investigators did not set limits for tidal volumes. A weaning protocol governed both limbs.

Results: the primary outcome was in-hospital mortality. The study was stopped early because of increased risk in the study group. At the time of termination, 571 patients had been enrolled, of whom 548 had undergone randomization: 275 to the HFOV group and 273 to the control-ventilation group. A total of 129 patients (47%) in the HFOV group, as compared with 96 patients (35%) in the control group, died in the hospital (relative risk of death with HFOV, 1.33; 95% confidence interval, 1.09 to 1.64; P=0.005) – an absolute risk INCREASE of 12%! This was independent of any other risk factor other than HFOV and was consistent at 28 days. Indeed 28 day mortality was 40% in HFOV group (which is not particularly bad) versus 29% (which is really excellent) in the conventional ventilation group – absolute risk increase 11% – number needed to injure 9. The duration of hospital stay for survivors was, on average, 5 days fewer in the CV group (although statistical significance is not reported) 25 versus 30 days.

Did HFOV have a physiological effect? Yes – patients almost immediately needed more vasopressors, more sedation and more neuromuscular blockade. There were fewer cases of refractory hypoxaemia but this had no statistically significant impact on outcomes.

My Impression

So, what to make of this study? Firstly, let us be clear – this was an excellent study (that we were all awareards of) performed by experts in the field of mechanical ventilation, who have a long track record of publication and interest in HFOV. They were not expecting the published results. This is a significant setback to our understanding of ARDS and interventions to rescue patients from severe hypoxaemia. Among my critical care colleagues, there are those of us who are proponents of ARPV and those of us who use HFOV. The published results ask as many questions about APRV as they do about oscillation. Can the worse outcomes be explained by increased doses of vasopressors and more sedation? No, I don’t believe it to be so: it is inconceivable that increased drug utilization could explain an 11% risk increase at 28 days. It is more likely that HFOV exacerbates ventilator induced lung injury (VILI).


The OSCAR study took place in the UK and included nearly 800 patients that had PF ratio <200 and wereOscar randomized to HFOV or CV. There was no significant between-group difference in the primary outcome, death at 28 days, which occurred in 166 of 398 patients (41.7%) in the HFOV group and 163 of 397 patients (41.1%) in the conventional-ventilation group (P=0.85). In other words – HFOV did not benefit these patients. Patients enrolled in this study had an average Apache II of 21 – lower than Oscillate – but had equally bad gas exchange when recruited. Although there was an increase in the use of muscle relaxants, there was no evidence of increased vasopressor requirements.

Of interest, patients in OSCAR had similar (although worse) 28 day mortality rates to those in the HFOV arm of the OSCILLATE study. It is worth looking at the LOV and EXPRESS trials for comparison. The EXPRESS trial had slightly older patients (60y both groups) with better gas exchange – PF ratio 143 and 144. Twenty eight day mortality was 31.2% and 27.8% (lower in high PEEP approach but not significant). The LOV study had patients in the same age range as both of these studies, but the PF ratios were significantly higher (144 in both groups); Apache II scores were 24 and 25 (patients were sicker than OSCAR). Mortality rates for all cause in hospital were 36.4% and 40.4% (again not significant). The lower end outcome is similar to the conventional group (and indeed had similar vent strategy to that group) in OSCILLATE. This suggests that the better outcomes in the conventional group in OSCILLATE accurately reflect true outcomes, and that the 28 day mortality in the LOV trial over-estimates outcomes at hospital discharge. But, can the difference in gas exchange really explain why the outcomes in OSCAR, in the conventional group at least, were 10% worse than EXPRESS? I don’t know – but comparing OSCILLATE to OSCAR – a 29% 28 day mortality (similar to LOV) is substantially lower than the 41% in the UK trial. These data suggest that the conventional group in that study did worse than expected. And, if this were the case, then HFOV was harmful in the OSCAR study too: the mortality rate for HFOV was essentially the same in both studies. Ok that might be conjecture – but take my point: a 41% mortality rate for ARDS is very high in the setting of a randomized controlled trial. For example, in the original ARMA trial the mortality rate in the control group (high TV) was 39.8% versus 31%; PF ratios 138 and 134. In the ALVEOLI trial the mortality rates were 24.9% (high PEEP) and 27.5%; PF ratios were 165 and 154. I have long argued that many of the patients in the NIH studies probably didn’t have ARDS – but the outcomes in OSCAR are the worst published in a multi center trial since the control group in Aries. Whatever way you look at it – this is all BAD NEWS for HFOV.

HFOV – is it safe?

One striking thing about these studies is how much the conflict with a previous meta-analysis of previously published papers. In that paper eight randomized controlled trials (n=419 patients) were included; the majority of patients had ARDS. Patients on HFOV had better oxygenation and reduced mortality (risk ratio 0.77, 95% confidence interval 0.61 to 0.98, P=0.03; six trials, 365 patients, 160 deaths). These results conflict directly with the outcomes of OSCILLATE and OSCAR: it is scary how meta-analysis of small studies (publication bias) can be misleading.

So, is it time to wrap up your oscillator and consign it to the ventilator graveyard? For ARDS – for routine practice – I think so.

1-forward-2-backFor rescue therapy or as a bridge to ECMO – HFOV may still have a role. Oscillation remains a useful therapy for broncho-pleural fistula and perhaps for severe lung contusion. But in other settings – I believe – use with extreme care. Is it time for a complete re-evaluation of open lung approaches in ARDS? Perhaps so – certainly before we put patients on extreme IRV modes (such as APRV) or HFO we should ask – “have I maxed out my options with conventional ventilation?”
One Step Forward – Two Steps Back.

Beachchair and Blood Pressure

BeachChairMAPIt is now more than 5 years since the Anesthesia Patient Safety Foundation highlighted the risk of central nervous system injury following anesthesia for shoulder surgery (SS) in the Beachchair position (BCP) (click here). Although we can never be certain, it appears likely that such injuries – principally devastating stroke, results from hypoperfusion and watershed ischaemia. Most anesthetists agree that, in the seated position, the mean arterial pressure as measured by a brachial cuff, under-estimates the pressure at the circle of Willis by 15mmHg or more. The safe lower range of MAP with regard to cerebral auto regulation remains unclear, but it is certainly not below 50mmHg (click here). Regardless, if we are to believe in the “Waterfall” effect of blood pressure, then a MAP of 65mHg from an arm BP cuff is marginal. If an arterial line is place – a procedure rarely performed in orthopedic shoulder patients – the transducer should be sited at the external auditory meatus. Although there are proponents for cerebral oximetry as a monitor in this setting – I do not believe that data are sufficient to demonstrate sensitivity and specificity of this device (here). The majority of experts in the field agree that the best option is to keep BP as close to baseline as possible if general anesthesia is administered for SS in BCP (here here and here). Clearly – “induced hypotension” is a bad idea in this setting. Also, the placement of the BP cuff on the leg or ankle (so that it does not cut of the iv line periodically) would appear most unwise. In one paper from Korea (click here), ankle blood pressure was substantially higher (up to 30mmHg for systolic pressure, 20mmHg mean pressure) compared with brachial pressure in the Beachchair position. In other words – if you are using an ankle cuff, the measured blood pressure (MAP) may be 35mmHg or more higher than the pressure seen at the circle of Willis.

My own practice is to use a brachial cuff and administer a phenylephrine infusion to keep the MAP above 75mmHg (or at the normal awake range for the patient). This appears to be the best approach based on my reading of the literature and available technologies. I would urge orthopedic anesthetists in the West to read the articles referenced here and come up with their own protocols. Comments?

Transfusion Strategy – Think Restrictive

nejm_transf_1.2013A half generation ago, the TRICC trial (here) suggested that routine blood transfusion in critically ill patients did not confer benefit if the haemoglobin level was above 7g/dl. This resulted in a evidence based paradigm for lower transfusion triggers. The problem was – how do you deal with the bleeding patients?
A recent study in NEJM (here) looked at liberal versus restrictive transfusion practices on patients admitted with gastrointestinal bleeding.

921 patients with severe acute upper gastrointestinal bleeding were included in the study: and 461 of them were randomly assigned to a restrictive strategy (transfusion when the hemoglobin level fell below 7 g per deciliter) and 460 to a liberal strategy (transfusion when the hemoglobin fell below 9 g per deciliter). Randomisation was stratified according to the presence or absence of hepatic cirrhosis.

Substantially more patients in the liberal strategy group received transfusion: 395 (85%)  versus 236  (49%) liberal versus restrictive (P<0.001). The conventional wisdom would hold that greater oxygen carrying capacity in the liberal group would result in better outcomes. The null hypothesis would be that there was no difference. However, the patients in the restrictive group had BETTER OUTCOMES. The hazard ratio for 6 week mortality was 0.55; 95% confidence interval [CI], 0.33 to 0.92; P=0.02) [with HR a number of <1 reflects benefit, >1 reflects injury]. The absolute risk reduction was 4% (5% restrictive, 9% liberal p = 0.02; NNT 25). In addition, patients in the liberal strategy group had a 6% absolute increase (number needed to injure 16; (P=0.01) ) in the risk of further bleeding.
There was an absolute risk reduction of adverse events of 8% in the restrictive group (NNT 12; p = 0.02). Restrictive transfusion also resulted in better survival in patients with peptic (gastric or duodenal) ulcers, and those with mild to moderate cirrhosis.

Why would bleeding patients do better if transfusions are witheld? There are many potential reasons: 1. The concept of damage control resuscitation: teleologically we have evolved to handle hypovolaemia and can survive considerable blood loss. Blood transfusion without source control may cause clots to destabilise and further bleeding to occur. 2. Blood is immunosuppressive: patients who are transfused are at elevated risk of infectious complications. 3. In this particular study patients in the liberal transfusion group had higher portal pressures and were more likely to rebleed (but so too were patients with peptic ulcers). 4. Transfusion may result in volume overload, abdominal compartment syndrome, myocardial ischaemia and transfusion related lung injury.

What are the implications of this study. Approach with caution! This study does not license clinicians to withhold blood from ex-sanguinating patients. Nor does it prove anything about transfusion in the setting of non gastrointestinal blood loss. However, it does provide us with further information about the safety and implications of blood transfusion in a specific setting. Allied with accumulating data detailing the hazards of colloid transfusion, adverse outcomes associated with crystalloid over-resuscitation, and the ongoing controversy regarding albumin – one has to wonder where we are with fluid resuscitation. Remembering that red cell transfusion is a key component of the Rivers’ surviving sepsis protocol, one wonders if this is the first real nail in the coffin for that approach.

Comments are welcome here.