Stay mean with the red stuff in septic shock

  • October 4, 2014

TRISS

Narrowing down the TRICC concept to septic shock patients, the TRISS trial looked at a transfusion trigger of 7 g/dl or 9 g/dl, using leuco-depleted blood, for the first 90 days of admission. Multi-centre, parallel-grouped and sensibly powered (over 1000 patients), they achieved good separation of Hb values.

No mortality difference at 90 days. No greater ischaemic events in the lower group and no increased use of life-support elements. But also no deleterious effects of giving blood were noticed – was this because leuco-depleted blood was used (unlike TRICC)?

Strikingly 36% of the higher threshold group were transfused, 2% of the lower.

Possible issues: not blinded, high baseline mortality rate (45% – cf ARISE, although illness severity measured with SOFA/SAPS v APACHE), difficulty picking up ischaemic events (non-protocolised diagnosis), actively infarcting patients were excluded. In the lower threshold group the patient could be transfused if ischaemic and the doctor felt it was wise but it’s not clear whether this happened.

Aside from the clinical lesson, does the very low need for blood in the ‘lower’ group suggest that there is a concerted physiological resetting of the haemoglobin target by the body itself (7ish), and we meddle with that in our correct-the-numbers tendency?

Subgroup analyses to come no doubt.

Awareness of awareness – NAP5 ICU section

  • October 2, 2014

aware clipThe recent National Audit Project looked at accidental awareness during general anaesthesia (AAGA). There was a (small) section on ICU/ED.

On the whole clear-headed awareness in the ICU is to be encouraged but hypnosis and sedation need to be taken seriously when required.

Almost all our sedative/induction drugs have some negative effects on the circulation. The balance of physiological upset ‘v’ risk of awareness more acute in ICU.

Principles

Induction:

  • Standard doses often dangerous and compounded by mechanical effect of ventilation.
  • Patient may be obtunded to start with.
  • Difficult airway relatively more common.

Recent study of 472 ICU intubations – almost all used propofol, mean dose was approx 100mg

Procedures:

  • Usually intravenous sedation.
  • Often no anaesthetic machines.
  • Difficult end-points where the patient was already obtunded.

Transfers:

  • Sedation maybe sufficient in calm environment but motion/noise can be stimulating.
  • Monitoring may suffer from movement artefact

 

NAP5 findings

10 cases related to ICU. 3 were patients during transfer post-operatively. 7 cases were on ICU or in ED (2.3%). 5 were morbidly obese.

Induction: 3 cases, all had muscle relaxant – in one case this was the only drug used (collapse and apparent unconsciousness). Low doses of propofol. One difficult intubation.

Maintenance: 2 were shortly after induction. 2 were during invterventions. All had muscle relaxants and iv infusion sedation. All had overall short time on vent and reported awareness pretty soon after waking. Possible effect of pre-morbid tolerance of opiate and benzos.

Transfers: 3 patients transferred from theatre on infusions. All with muscle relaxant.

Patient experience: 2 had paralysis and distress but no pain. 5 reported paralysis and distress and pain.

Summary points

The numbers and proportions in this section of NAP 5 are probably not of value (presumably often awareness is ‘forgotten’ in prolonged illness), but there are some core messages:

  • In critical illness low GCS does not always equate to low likelihood of awareness
  • Sedation end-points are often not available or reliable.
  • Neuromuscular blockade is a risk.
  • Cardiovascular instability should be solved first where possible. Consider induction/sedation agents that cause less hypotension.
  • All reports involved distress (cf anaesthesia) – so expect longer term psych sequelae and support these patients. The critically ill are already a group prone to this.
  • Don’t delay starting infusions post-intubation. Consider TCI infusions. Use intubation checklists that include post-procedure sedation elements.

Research suggestions: DOA monitoring in ICU, TCI use in ICU, preferential use of sedatives with sympathomimetic properties (e.g. Ketamine).

AAGA in ICU/ED may not be completely avoidable. Apparent level of consciousness may be misleading – e.g. in the exhausted, neurologically injured or psychologically impaired.

Addressing each of analgesia/sedation/hypnosis/paralysis/hypotension in appropriate proportion and avoid both the potentially deleterious pressor response and potentially psychologically disabling awareness, while limiting circulatory upset.

 

New ESC PE guidelines – still muddled in the middle?

  • September 26, 2014

RV overload The new European PE guidelines from the ESC appear to start applying some of the evidence regarding patients without shock but with RV strain and elevated troponin/BNP.

Remember the sPESI – 1 point for: cancer, COPD, chronic heart failure, age >80, sats<90%. Any of these put the patient into the intermediate (30 day mortality) risk group at least. This group is divided into intermediate-high and intermediate-low using the presence of RV dysfunction (or dilatation) and elevated troponin/BNP. However no clear therapeutic reason for the division is given.

PE algorithmIdeally CT angiogram, but echo is emphasised as the imaging of choice where time or facilities are lacking.

500 ml fluid bolus is considered enough. Brief discussion of inotropes and pressors: noradrenaline (an RV inotrope) if hypotensive with adequate cardiac output, maybe dobutamine if more cardiac output required, adrenaline for a ‘balanced’ approach.

Ventilation should be expected to worsen venous return and RV function, so avoid or approach very cautiously and limit pressures accordingly.

Thrombolysis:

  • Thrombolyse high risk and accept the 1-2% haemorrhage risk.
  • Don’t thrombolyse anyone else routinely.
  • Watch the intermediate-high risk group closely to pick up transition into shock/high-risk.
  • Catheter-directed thrombolysis requires experts but is well-regarded if light on evidence.

If high risk and thrombolysis is contraindicated:

  • Rheolytic/suction/rotational thrombectomy or catheter fragmentation by an expert.
  • Surgical embolectomy should be done where there is good experience.

Anticoagulation remains the mainstay with the novel oral anticoagulants now beginning to look superior in terms of safety ‘v’ vitamin K antagonism.

IVC filters are short on evidence. Little choice if anticoagulation is contraindicated but surgery not warranted. May reduce recurrence of PE but increase DVT.

So despite these comprehensive guidelines delineating the intermediate-high risk group there is no firm belief that thrombolysis is the right thing. Fancy a half-dose?

 

Dying sooner or later? Predictors of pre-30 day mortality versus post-90 day

  • September 16, 2014

30v90tableHypothesizing that the determinants of death within 30 days of admission to ICU are different to those for death after 90 days, Garland et al looked at a Canadian 11 ICU registry. We’re familiar with survival curves levelling to population baseline rate after a few months (if you can make it 3 months it’s almost like it never happened!). Examining the curve between 1 and 90 days the section before 30 days is considerably steeper. So unsurprisingly early deaths relate to type and severity of the critical illness whereas by about day 90 co-morbidities have become the stronger predictor. Age was again a weak marker.

Perhaps sometime we forget that for patients with multiple concurrent medical problems their ‘pre-ICU’ Kaplan-Meier was already pretty steep. If we get them through 3 months, they rejoin their potentially ill-fated subgroup curve.

Does this suggest we should stop looking at 30 day mortality rates and make 90 day survival our default primary outcome when choosing our evidence?

The difficulty of ‘futility’

  • September 8, 2014

Futility tableUsing local consensus on the definition of futile, Huynh et al have returned to suggest and quantify an ‘opportunity cost’ (i.e. a detriment to others due non-futile care) incurred.

At a single centre, 5 unit hospital, delay in admission from A&E and delay in transfer to a tertiary ICU were examined and the impact of futile care on these delays assessed.

‘Futile’, ‘probably futile’ and non-futile treatment were not clearly defined and were subjective to the extent of depending on the specific coincidence of patient, doctor and hospital state of busyness. The same group has previously published on the same topic, finding that, in their single centre experience approximately 7% of hospital patient days were spent delivering costly futile care. 15% of those receiving futile care were still alive 6 months later but generally with a low quality of life. It is not clear in this week’s article how many patients were directly affected by delay in treatment, or to what detriment. In addition, figures from these studies will not be directly applicable to your institution, but the principles are intuitive and are likely to be transferable to some degree. It is surely no surprise that on less busy days there was a greater proportion of patients receiving futile treatment.

However, how often is it clear that treatment on the unit is futile in an absolute sense? Does the slippery term ‘futile’ really have a different definition for any given day/unit/doctor? Do we really operate a first-come-first-served system? The last chance to eke out what might be a tiny percentage chance to return to an acceptable life is often requested of intensivists. We know we are often a poor judge of the chance of success and also what an acceptable outcome is. Moreover, do some patients have a ‘better death’ on ICU, and if so is that of calculable value?

Immuno-nutrition worse than useless?

  • August 31, 2014

ImmunonutritionHeyland, SIGNET, REDOXS, ARDNSNET’s OMEGA, INTERSEPT, and now the Metaplus study. 

Approximately  300 patients, critically ill (APACHE >15) and ventilated were all given high protein (>1.2g/Kg/day), normal calorie (25Kcal/Kg/day) feed, either with or without Omega-3 acids, glutamine and antioxidants. All were started within 48 hours and stopped within 28 days.

No benefit in terms of length of stay or days on the ventilator. No difference in infection. No difference in subgroups except for an increase in adjusted (for age and disease severity) 6 month mortality amongst the medical patients.

Whilst most agree on high protein feeding, and initial permissive hypocaloric (~trophic) nutrition, evidence on the remaining contents is unclear. Regarding micronutrients Selenium recently performed well, but otherwise there have been no convincing and repeatable successes. And now it looks like the current batch of immuno-nutrition candidates have fallen short. Vitamin D is currently ‘research en-vogue’ but not yielding impressive results even at the basic science level, evident in another paper this week.

Moreover, the ‘ventilated patient’ is a heterogeneous set. Nutrients have been given enterally in some trials and parenterally in others. As always, larger studies in more defined subgroups are yet to happen.

The earlier the better? Maybe, maybe not for renal replacement therapy.

  • August 23, 2014

RRT timing

In this recent re-look at patients from a previous seminal study, a ‘nested’ cohort from the RENAL study with RIFLE ‘I’ acute kidney injury (GFR<50%, creatinine rise to twice baseline, UOP <0.5ml/kg for 12hr).were selected.

The APACHE III score for those supported late was significantly lower suggesting there may have been something different (a covariate, so not propensity matched) that added to confidence in delaying RRT.

Moreover only about 40% of those supported early had sepsis, against 60% of those receiving RRT after 48hr. This possibly reflects an element of faith in source control and circulatory support – give resuscitation a chance before firing up the filter. Presumably they were also less likely to be fluid overloaded, an indication for RRT know to carry poor outcome.

Urea level does not correlate well with time from start of AKI using RIFLE criteria. This is an issue that needs to be considered when looking at other studies on the same subject.

Acknowledging the dangers in concluding causality in observational studies, earlier RRT was not significantly associated with improved outcome but there was a suggestion of benefit (a trend towards mortality if delayed) that needs more exploring; large prospective studies in groups eg severe sepsis.

Do the dosing studies then need to be redone as well? An interesting single unit experience in saving money by switching to low volume (20ml/kg/hr) CVVHDF without changing clinical outcome was published this week.

Staffing the unit – more questions than answers?

  • August 19, 2014

UK staffing survey tableA number of articles in the last few months have focused on staffing structure in the ICU.

Previously we’ve seen that ‘high intensity staffing‘  (a dedicated ICU team, or at least the obligatory consultation by one) reduces mortality, in the USA. However night-time intensivists don’t seem to do the same unless there’s a ‘low intensity’ daytime staffing model. Cross-covering fellows may even improve outcome, perhaps through a ‘second opinion’ effect, as suggested in a single centre study.

Now in England, after the recent core standards (ICS and ESICM), a national survey suggests neither consultants’ working pattern nor clinical experience affect mortality (adjusted). Grade of covering night doctor again appeared not to correlate with outcome. The suggestion that intensivist involvement in handover is associated with mortality can almost certainly be ignored as chance (given the small proportion where there is no involvement). Particularly as cardiac arrest in the preceding 24 hours seemed not to make a difference!

Telemedicine  has also shown promising results across the Atlantic in a recent meta-analysis.

Perhaps a bigger issue is staff at the bedside. Isn’t it likely that nursing staffing ratios and continuity affect clinical measures? And how do critical care practitioners and trainees fit into these results?

In any case, aren’t mortality statistics a blunt tool for this analysis? Clinically, longer term outcome measures, readmission rates and other quality indicators may be better. The organisational and meta-outcomes such as staffing moral, staff retention, patient and family satisfaction, and the trainees experience may be better still.