Category Archives: ICU

Stuff relevant to patients on ICU

Age adjusted D-dimer cut-off values

Age adjusted D-dimer cut-off values (age×10 µg/L) improve specificity without losing sensitivity for venous thromboembolism. This could spare many elderly patients unnecessary imaging. Full text is available free from the BMJ.
Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis>
BMJ. 2013 May 3;346:f2492
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OBJECTIVE: To review the diagnostic accuracy of D-dimer testing in older patients (>50 years) with suspected venous thromboembolism, using conventional or age adjusted D-dimer cut-off values.

DESIGN Systematic review and bivariate random effects meta-analysis.

DATA SOURCES: We searched Medline and Embase for studies published before 21 June 2012 and we contacted the authors of primary studies.

STUDY SELECTION: Primary studies that enrolled older patients with suspected venous thromboembolism in whom D-dimer testing, using both conventional (500 µg/L) and age adjusted (age × 10 µg/L) cut-off values, and reference testing were performed. For patients with a non-high clinical probability, 2 × 2 tables were reconstructed and stratified by age category and applied D-dimer cut-off level.

RESULTS: 13 cohorts including 12,497 patients with a non-high clinical probability were included in the meta-analysis. The specificity of the conventional cut-off value decreased with increasing age, from 57.6% (95% confidence interval 51.4% to 63.6%) in patients aged 51-60 years to 39.4% (33.5% to 45.6%) in those aged 61-70, 24.5% (20.0% to 29.7% in those aged 71-80, and 14.7% (11.3% to 18.6%) in those aged >80. Age adjusted cut-off values revealed higher specificities over all age categories: 62.3% (56.2% to 68.0%), 49.5% (43.2% to 55.8%), 44.2% (38.0% to 50.5%), and 35.2% (29.4% to 41.5%), respectively. Sensitivities of the age adjusted cut-off remained above 97% in all age categories.

CONCLUSIONS: The application of age adjusted cut-off values for D-dimer tests substantially increases specificity without modifying sensitivity, thereby improving the clinical utility of D-dimer testing in patients aged 50 or more with a non-high clinical probability.

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Restricting transfusion in upper GI bleeding

Improved outcomes and reduced complications were associated with a restrictive transfusion strategy in patients with upper gastrointestinal bleeding. Note that patients with “massive exsanguinating bleeding” were excluded from the study so this shouldn’t be extrapolated to such presentations.
The benefit seemed to be most marked in patients with variceal haemorrhage, but not those with the most severe Child-Pugh class. In portal hypertensive-related bleeding, transfusion may increase portal pressure and exacerbate bleeding.
The patients were ‘scoped within 6 hours, and less than 10% received FFP or platelets. Both groups averaged over 5 litres of crystalloid in the first 72 hours.
Transfusion Strategies for Acute Upper Gastrointestinal Bleeding
N Engl J Med. 2013 Jan 3;368(1):11-21
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BACKGROUND: The hemoglobin threshold for transfusion of red cells in patients with acute gastrointestinal bleeding is controversial. We compared the efficacy and safety of a restrictive transfusion strategy with those of a liberal transfusion strategy.

METHODS: We enrolled 921 patients with severe acute upper gastrointestinal bleeding and randomly assigned 461 of them 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). Randomization was stratified according to the presence or absence of liver cirrhosis.

RESULTS: A total of 225 patients assigned to the restrictive strategy (51%), as compared with 61 assigned to the liberal strategy (14%), did not receive transfusions (P<0.001) [corrected].The probability of survival at 6 weeks was higher in the restrictive-strategy group than in the liberal-strategy group (95% vs. 91%; hazard ratio for death with restrictive strategy, 0.55; 95% confidence interval [CI], 0.33 to 0.92; P=0.02). Further bleeding occurred in 10% of the patients in the restrictive-strategy group as compared with 16% of the patients in the liberal-strategy group (P=0.01), and adverse events occurred in 40% as compared with 48% (P=0.02). The probability of survival was slightly higher with the restrictive strategy than with the liberal strategy in the subgroup of patients who had bleeding associated with a peptic ulcer (hazard ratio, 0.70; 95% CI, 0.26 to 1.25) and was significantly higher in the subgroup of patients with cirrhosis and Child-Pugh class A or B disease (hazard ratio, 0.30; 95% CI, 0.11 to 0.85), but not in those with cirrhosis and Child-Pugh class C disease (hazard ratio, 1.04; 95% CI, 0.45 to 2.37). Within the first 5 days, the portal-pressure gradient increased significantly in patients assigned to the liberal strategy (P=0.03) but not in those assigned to the restrictive strategy.

CONCLUSIONS: As compared with a liberal transfusion strategy, a restrictive strategy significantly improved outcomes in patients with acute upper gastrointestinal bleeding. (Funded by Fundació Investigació Sant Pau; ClinicalTrials.gov number, NCT00414713.).

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Potential new therapy for acute heart failure

Interesting new drug to know about: Serelaxin, recombinant human relaxin-2. It’s hard to assess the clinical significance of the statistically significant findings. Let’s see if a benefit is replicated in future studies. It’s hard to imagine a normotensive patient that can’t be fixed with existing therapies though.
Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial.
Lancet. 2013 Jan 5;381(9860):29-39
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BACKGROUND: Serelaxin, recombinant human relaxin-2, is a vasoactive peptide hormone with many biological and haemodynamic effects. In a pilot study, serelaxin was safe and well tolerated with positive clinical outcome signals in patients with acute heart failure. The RELAX-AHF trial tested the hypothesis that serelaxin-treated patients would have greater dyspnoea relief compared with patients treated with standard care and placebo.

METHODS: RELAX-AHF was an international, double-blind, placebo-controlled trial, enrolling patients admitted to hospital for acute heart failure who were randomly assigned (1:1) via a central randomisation scheme blocked by study centre to standard care plus 48-h intravenous infusions of placebo or serelaxin (30 μg/kg per day) within 16 h from presentation. All patients had dyspnoea, congestion on chest radiograph, increased brain natriuretic peptide (BNP) or N-terminal prohormone of BNP, mild-to-moderate renal insufficiency, and systolic blood pressure greater than 125 mm Hg. Patients, personnel administering study drug, and those undertaking study-related assessments were masked to treatment assignment. The primary endpoints evaluating dyspnoea improvement were change from baseline in the visual analogue scale area under the curve (VAS AUC) to day 5 and the proportion of patients with moderate or marked dyspnoea improvement measured by Likert scale during the first 24 h, both analysed by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00520806.

FINDINGS: 1161 patients were randomly assigned to serelaxin (n=581) or placebo (n=580). Serelaxin improved the VAS AUC primary dyspnoea endpoint (448 mm × h, 95% CI 120-775; p=0·007) compared with placebo, but had no significant effect on the other primary endpoint (Likert scale; placebo, 150 patients [26%]; serelaxin, 156 [27%]; p=0·70). No significant effects were recorded for the secondary endpoints of cardiovascular death or readmission to hospital for heart failure or renal failure (placebo, 75 events [60-day Kaplan-Meier estimate, 13·0%]; serelaxin, 76 events [13·2%]; hazard ratio [HR] 1·02 [0·74-1·41], p=0·89] or days alive out of the hospital up to day 60 (placebo, 47·7 [SD 12·1] days; serelaxin, 48·3 [11·6]; p=0·37). Serelaxin treatment was associated with significant reductions of other prespecified additional endpoints, including fewer deaths at day 180 (placebo, 65 deaths; serelaxin, 42; HR 0·63, 95% CI 0·42-0·93; p=0·019).

INTERPRETATION: Treatment of acute heart failure with serelaxin was associated with dyspnoea relief and improvement in other clinical outcomes, but had no effect on readmission to hospital. Serelaxin treatment was well tolerated and safe, supported by the reduced 180-day mortality

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Blood products in trauma & survivor bias

Esky-label.001The observation that patients with haemorrhagic trauma in military and civilian settings do better if they receive coagulation factors and platelets is yet to be replicated in a randomised trial. It has been suggested that the effect may in part be a consequence of survivor bias – ie. that if a patient lives long enough to received some thawed fresh frozen plasma, then they were already more likely to be a survivor and therefore more survivors will be represented in the ‘FFP’ groups vs a ‘no-FFP’ comparison group.
An attempt to eliminate survivor bias was made in the PROMMTT study, which documented the timing of transfusions during active resuscitation and patient outcomes in adult trauma patients who received a transfusion of at least 1 unit of RBCs within 6 hours of admission.
Increased ratios of plasma:RBCs and platelets:RBCs were independently associated with decreased 6-hour mortality, when haemorrhagic death predominated. In the first 6 hours, patients with ratios less than 1:2 were 3 to 4 times more likely to die than patients with ratios of 1:1 or higher.
A prospective trial is underway to identify the optimal ratio of blood products, in the PROPPR study, in which 1:1:1 ratio of plasma:platelets:RBC will be compared with 1:1:2.
The Prospective, Observational, Multicenter, Major Trauma Transfusion (PROMMTT) Study
Arch Surg. 2012 Oct 15:1-10
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Objective: To relate in-hospital mortality to early transfusion of plasma and/or platelets and to time-varying plasma:red blood cell (RBC) and platelet:RBC ratios.

Design: Prospective cohort study documenting the timing of transfusions during active resuscitation and patient outcomes. Data were analyzed using time-dependent proportional hazards models.

Setting: Ten US level I trauma centers.
Patients: Adult trauma patients surviving for 30 minutes after admission who received a transfusion of at least 1 unit of RBCs within 6 hours of admission (n = 1245, the original study group) and at least 3 total units (of RBCs, plasma, or platelets) within 24 hours (n = 905, the analysis group).

Main Outcome Measure: In-hospital mortality.

Results: Plasma:RBC and platelet:RBC ratios were not constant during the first 24 hours (P < .001 for both). In a multivariable time-dependent Cox model, increased ratios of plasma:RBCs (adjusted hazard ratio = 0.31; 95% CI, 0.16-0.58) and platelets:RBCs (adjusted hazard ratio = 0.55; 95% CI, 0.31-0.98) were independently associated with decreased 6-hour mortality, when hemorrhagic death predominated. In the first 6 hours, patients with ratios less than 1:2 were 3 to 4 times more likely to die than patients with ratios of 1:1 or higher. After 24 hours, plasma and platelet ratios were unassociated with mortality, when competing risks from nonhemorrhagic causes prevailed.

Conclusions: Higher plasma and platelet ratios early in resuscitation were associated with decreased mortality in patients who received transfusions of at least 3 units of blood products during the first 24 hours after admission. Among survivors at 24 hours, the subsequent risk of death by day 30 was not associated with plasma or platelet ratios.

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TracMan results

The TracMan trial – a multicentre randomised trial of early vs late tracheostomy in ICU patients – has been published, showing no difference in the primary outcome of mortality.
A review of the trial is posted on the excellent PulmCCM blog:

There was no proven difference between groups in 30-day mortality (30.8% early vs. 31.5% late, primary outcome), nor in any other outcome including 2-year mortality.

Patients getting early tracheostomies required fewer days of sedation, and there was a suggestion of a reduction of -1.7 ventilator days with early trach (mean 13.6 days vs 15.2 days, p=0.06). However, ICU stays were exactly equal at a median 13 days.

Also, 7% of patients had significant bleeding attributed to their tracheostomies (defined as needing IV fluids or another intervention); this amounted to 11 patients in the early group and 8 in the late group.

PulmCCM is an excellent free resource that will deliver critical care updates to your inbox. It has a number of other useful features, like free board review questions – highly recommended!
Effect of early vs late tracheostomy placement on survival in patients receiving mechanical ventilation: the TracMan randomized trial
JAMA. 2013 May 22;309(20):2121-9
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IMPORTANCE: Tracheostomy is a widely used intervention in adult critical care units. There is little evidence to guide clinicians regarding the optimal timing for this procedure.

OBJECTIVE: To test whether early vs late tracheostomy would be associated with lower mortality in adult patients requiring mechanical ventilation in critical care units.

DESIGN AND SETTING: An open multicentered randomized clinical trial conducted between 2004 and 2011 involving 70 adult general and 2 cardiothoracic critical care units in 13 university and 59 nonuniversity hospitals in the United Kingdom.

PARTICIPANTS: Of 1032 eligible patients, 909 adult patients breathing with the aid of mechanical ventilation for less than 4 days and identified by the treating physician as likely to require at least 7 more days of mechanical ventilation.

INTERVENTIONS: Patients were randomized 1:1 to early tracheostomy (within 4 days) or late tracheostomy (after 10 days if still indicated).

MAIN OUTCOMES AND MEASURES: The primary outcome measure was 30-day mortality and the analysis was by intention to treat.

RESULTS: Of the 455 patients assigned to early tracheostomy, 91.9% (95% CI, 89.0%-94.1%) received a tracheostomy and of 454 assigned to late tracheostomy, 44.9% (95% CI, 40.4%-49.5%) received a tracheostomy. All-cause mortality 30 days after randomization was 30.8% (95% CI, 26.7%-35.2%) in the early and 31.5% (95% CI, 27.3%-35.9%) in the late group (absolute risk reduction for early vs late, 0.7%; 95% CI, -5.4% to 6.7%). Two-year mortality was 51.0% (95% CI, 46.4%-55.6%) in the early and 53.7% (95% CI, 49.1%-58.3%) in the late group (P = .74). Median critical care unit length of stay in survivors was 13.0 days in the early and 13.1 days in the late group (P = .74). Tracheostomy-related complications were reported for 6.3% (95% CI, 4.6%-8.5%) of patients (5.5% in the early group, 7.8% in the late group).

CONCLUSIONS AND RELEVANCE: For patients breathing with the aid of mechanical ventilation treated in adult critical care units in the United Kingdom, tracheostomy within 4 days of critical care admission was not associated with an improvement in 30-day mortality or other important secondary outcomes. The ability of clinicians to predict which patients required extended ventilatory support was limited.

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The non-intubation checklist

no-sm

Scenario:
A 79 year old previously well female presents with loss of consciousness, having been found unresponsive by her daughter who saw her well one hour previously.
Examination reveals a GCS of E1V2M3 = 6 and reactive pupils with no lateralising signs. She is hypertensive. A VBG reveals a normal glucose and sodium and a pCO2 of 60 mmHg (7.9 kPa).
The emergency physician’s plan is to intubate and get a CT scan of her brain. This is explained to the daughter.
A no-brainer? You’d think so.

A consistent issue that recurs during discussions with UK emergency medicine colleagues is that of having to rely on anaesthesia and/or ICU colleagues for intubation of their patients in the ED. The pain comes not from disagreeing about who does the procedure or what drugs to use, but rather on the decision to intubate.
The refusal to intubate can stall or halt a resuscitation plan, delay care, result in risky transfers to the imaging suite, and even deny potential outcome-improving therapy (for example post-ROSC cooling). It can undermine team leadership and disrupt the team dynamic.
There are often different ways to ‘skin a cat’ and it is frequently helpful to invite the opinion of other critical care specialists. However, it is clear from multiple discussions with frustrated EM colleagues that the decision not to intubate is often influenced by non-clinical factors, most often ICU bed availability. Other times, it appears to be that the ‘gatekeeper’ to airway care (and to ICU beds) does not share the same appreciation of the clinical issues at stake. Examples here include the self-fulfilling pessimism post-ROSC based on inappropriate assignment of predictive value to neurological signs, and the assumption of non-treatable pathology in elderly patients presenting with coma.
The obvious solution to this is that the responsibility for managing the ‘A’ of ABC should not be delegated to non-emergency medicine personnel. Sadly, this is not achievable 24/7 in all UK departments right now for a number of awkward reasons.
So what’s a team leader to do when faced with a colleague’s refusal to intubate? The best approach would be to gently and politely persuade them to change their mind by stating some clinical facts that enable a shared mental model and agreed management plan, and to ensure the most senior available physicians are participating in the discussion.
Sometimes that fails. What next? Here’s a suggestion. This is slightly tongue-in-cheek but take away from it what you will.
It is imperative that the individual declining intubation appreciates the gravity of his or her decision. They must not be under the impression that they’ve done you (and the patient) a favour by giving their opinion after an ‘airway consult’. They have declined a resuscitative intervention requested by the emergency medicine team leader and should appreciate the consequences of this decision and the need to document it as such.
Perhaps say something along the lines of:

I see we haven’t managed to agree on this. We’ll just need you to complete the non-intubation form please for our quality improvement process. This will also help prevent your point being forgotten or misunderstood if we’re unlucky enough to face any complaints or litigation. I can fill it in on your behalf but I suspect you’d want to represent yourself as accurately as possible when documenting such a bold decision

And here’s the form. It is provocative, cheeky, and in no way should really be used in its current form:

nonintubationchecklistsm

Thenar eminence based medicine

A recent study showed superior effectiveness of one bag-mask ventilation style over another in novice providers. The technique recommended is the thenar eminence grip, in which downward pressure is applied with the thenar eminences while the four fingers of each hand pull the jaw upwards toward the mask.

Interestingly, in their crossover study in which the thenar emininence (TE) technique was compared with the traditionally taught ‘CE’ technique, they demonstrated a ‘sequence effect’. If subjects did TE first, they maintained good tidal volumes when doing CE. However if they did CE first, they achieved poor tidal volumes which were markedly improved when switching to TE.

The authors suggest: “A possible explanation for this sequence effect is that the TE grip is superior. When one used the TE grip first, he or she was more likely to learn how a good tidal volume “feels” and then more likely to apply good technique with the EC grip.“.

Some of us have been practicing and teaching this technique for a while. None have put it better than the brilliant Reuben Strayer of EM Updates in this excellent short video:

Emergency Ventilation in 11 Minutes from reuben strayer on Vimeo.

Efficacy of facemask ventilation techniques in novice providers
J Clin Anesth. 2013 May;25(3):193-7

STUDY OBJECTIVE: To determine which of two facemask grip techniques for two-person facemask ventilation was more effective in novice clinicians, the traditional E-C clamp (EC) grip or a thenar eminence (TE) technique.

DESIGN: Prospective, randomized, crossover comparison study.

SETTING: Operating room of a university hospital.

SUBJECTS: 60 novice clinicians (medical and paramedic students).

MEASUREMENTS: Subjects were assigned to perform, in a random order, each of the two mask-grip techniques on consenting ASA physical status 1, 2, and 3 patients undergoing elective general anesthesia while the ventilator delivered a fixed 500 mL tidal volume (VT). In a crossover manner, subjects performed each facemask ventilation technique (EC and TE) for one minute (12 breaths/min). The primary outcome was the mean expired VT compared between techniques. As a secondary outcome, we examined mean peak inspiratory pressure (PIP).

MAIN RESULTS: The TE grip provided greater expired VT (379 mL vs 269 mL), with a mean difference of 110 mL (P < 0.0001; 95% CI: 65, 157). Using the EC grip first had an average VT improvement of 200 mL after crossover to the TE grip (95% CI: 134, 267). When the TE grip was used first, mean VTs were greater than for EC by 24 mL (95% CI: -25, 74). When considering only the first 12 breaths delivered (prior to crossover), the TE grip resulted in mean VTs of 339 mL vs 221 mL for the EC grip (P = 0.0128; 95% CI: 26, 209). There was no significant difference in PIP values using the two grips: the TE mean (SD) was 14.2 (7.0) cm H2O, and the EC mean (SD) was 13.5 (9.0) cm H2O (P = 0.49).

CONCLUSIONS: The TE facemask ventilation grip results in improved ventilation over the EC grip in the hands of novice providers.

RSI haemodynamics in the field

intubated-prehosp-vol-iconThe noxious stimulus of laryngoscopy & tracheal intubation can precipitate hypertension, tachycardia, and intracranial pressure elevation, risking exacerbation of brain injury or haemorrhage. Physicians from an English Helicopter Emergency Medical Service examined the response of heart rate and blood pressure to prehospital rapid sequence intubation (RSI). While a retrospective study, the haemodynamic data were prospectively recorded and documented using standard monitor printouts, and time of intubation could be accurately determined by the onset of capnography recordings. Their standardised system documents blood pressure recordings every three minutes. Etomidate and suxamethonium were used for RSI.
They report their findings:


A hypertensive response occurred in 79% (70/89) of patients. MAP exceeded the upper limit of estimated intact cerebral autoregulation (150 mmHg) in 18% (16/89) of cases and 9% (8/89) of patients had a greater than 100% increase in MAP and/or SBP. A single hypotensive response occurred. A tachycardic response occurred in 58% (64/110) of patients and bradycardia was induced in one.

Of note, 97 of the 115 patients had injuries that included head trauma.
The authors note that opioids are often co-administered during in-hospital RSI and that this may offset the haemodynamic stimulation, while possible increasing the complexity of the procedure in the prehospital environment. They have modified their pre-hospital anaesthesia standard operating procedure to include the use of an opioid and will report the associated outcomes and complication rates ‘in due course’.
This is interesting and important stuff, and something we should all be looking at in our respective prehospital critical care services.
The haemodynamic response to pre-hospital RSI in injured patients
Injury. 2013 May;44(5):618-23
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BACKGROUND: Laryngoscopy and tracheal intubation provoke a marked sympathetic response, potentially harmful in patients with cerebral or cardiovascular pathology or haemorrhage. Standard pre-hospital rapid sequence induction of anaesthesia (RSI) does not incorporate agents that attenuate this response. It is not known if a clinically significant response occurs following pre-hospital RSI or what proportion of injured patients requiring the intervention are potentially at risk in this setting.

METHODS: We performed a retrospective analysis of 115 consecutive pre-hospital RSI’s performed on trauma patients in a physician-led Helicopter Emergency Medical Service. Primary outcome was the acute haemodynamic response to the procedure. A clinically significant response was defined as a greater than 20% change from baseline recordings during laryngoscopy and intubation.

RESULTS: Laryngoscopy and intubation provoked a hypertensive response in 79% of cases. Almost one-in-ten patients experienced a greater than 100% increase in mean arterial pressure (MAP) and/or systolic blood pressure (SBP). The mean (95% CI) increase in SBP was 41(31-51) mmHg and MAP was 30(23-37) mmHg. Conditions leaving the patient vulnerable to secondary injury from a hypertensive response were common.

CONCLUSIONS: Laryngoscopy and tracheal intubation, following a standard pre-hospital RSI, commonly induced a clinically significant hypertensive response in the trauma patients studied. We believe that, although this technique is effective in securing the pre-hospital trauma airway, it is poor at attenuating adverse physiological effects that may be detrimental in this patient group.

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Awake intubation

I had some fun today getting intubated.
We used the Ambu aScope 2 and the Greater Sydney Area HEMS equipment and approach to airway management. I didn’t receive an antisialogogue or any analgesia or sedation.
The big learning point for me was how hard it was to anaesthetise the posterior part of my nasal cavity and nasopharynx. I thought the worst part would be any stimulation of my vocal cords or trachea with lidocaine or instrumentation, but this really was fine. Nebulised 2% lidocaine (the strongest concentration we have), atomised lidocaine (using a mucosal atomiser), and co-phenylcaine spray weren’t sufficient. I can see why people use pastes or gel to maintain mucosal contact while the lidocaine takes effect, but we don’t have those (yet). The best solution came from hooking up oxygen tubing to an iv cannula via a three way tap. Oxygen was run through at 2 l/min and lidocaine injected via the the three way tap. This enabled an atomised spray to be directed right onto the area concerned, and made the insertion of the nasotracheal tube more tolerable – although still unpleasant.
crazed-nutter-sm
The fact I could be intubated awake with reasonable topicalisation suggests most patients should tolerate it perhaps after even an analgesic dose of ketamine, eg. 30-40 mg in an adult. I suspect full dissocation would not be required, which is good for cooperation (“stick your tongue out sir”). I appreciate there are better agents, such as remifentanil or dexmedetomidine, but my area of interest is the retrieval setting – where I have neither the luxury of using these agents nor that of calling for anaesthetic back up.
Thanks to HEMS physicians Emily Stimson, Nirosha De Zoysa, Felicity Day, Chloe Tetlow, and Fergal McCourt for making it fun and safe.
Here’s the video:

Twitter has been helpful in gathering some advice, particularly from @DocJohnHinds: