Graft versus Host Disease

A 34-year-old woman received a small bowel, pancreas and abdominal wall transplant.

Despite the operation being technically very difficult and prolonged, she initially recovered well after the procedure and her transplanted bowel started to work. However, after a few days she started developing respiratory complications eventually requiring re-intubation despite antibiotics. She went on to develop multi-organ dysfunction requiring vasopressor support and renal replacement therapy. Antifungals and co-trimoxazole were added, with no additional benefit noted.

A skin rash started to develop, which raised the suspicion of Graft versus Host Disease (GvHD). A diagnostic test was performed (chimerism of peripheral blood leucocytes), and it confirmed the diagnosis of GvHD.

Doses of immunosuppressants such as tacrolimus, mycophenolate mofetil were increased and steroids were started too.

An experimental therapy of mesenchymal stem cells infusion was also employed, but she continued to deteriorate further and she eventually died after a prolonged admission on ICU.

Graft versus Host Disease – what it is, how to diagnose it, how to treat itRead More »


Extracorporeal CO2 removal

A 42 year old man presented with a week-long history of increasing shortness of breath, cough  (productive of purulent sputum) and fevers on a background of significant chronic lung disease. He had a ten year history of interstitial lung disease and was on the waiting list for a lung transplant. He used oxygen at a rate of 2 litres per minute at home, 24 hours a day. His usual exercise tolerance of 200 metres had been significantly reduced for the past week. His regular medications included seretide and salbutamol inhalers, lansoprazole, azathioprine, prednisolone alendronate.

On arrival in hospital, he was alert and orientated. He had a patent airway, but was tachypnoeic (rate of 50/minute) using his respiratory accessory muscles and a tracheal tug was evident. An arterial blood gas revealed type two respiratory failure (pH 7.26; pO2 8.14, pCO2 7.52 on 15 liters/min of face mask oxygen). He was hypotensive (80/40mmHg) and tachycardic (130/minute, sinus rhythm). A pyrexia of 39.2°C was recorded. Blood results showed normal renal function, a slightly elevated white cell count of 14.

The patient was admitted to the high dependency for close monitoring in view of his history and presentation. He was commenced on treatment for a presumed infection (viral or bacterial) with oseltamivir, co-amoxiclav and clarithromycin and given three “pulsed” doses (750mg) of methylprednisolone. He remained stable for the next twelve hours.

Early the next morning, he became very hypoxic (oxygen saturations less than 50%), bradycardic (<35 beats per minute) and had a brief hypoxic respiratory arrest. He received 1 cycle of cardiopulmonary resuscitation and was intubated. There was subsequently a return of spontaneous circulation.

The next 24 hours involved a period of difficulty with ventilation. His peak airway pressures were very high, despite being paralysed and a low volume/high respiratory rate strategy being employed. He was discussed with a tertiary respiratory centre and it was decided that he should be transferred for insertion of a pumpless arteriovenous interventional lung assist (for extracorporeal carbon dioxide removal) as a bridge prior to lung transplantation. He had formal ultrasound measurement of his femoral arteries. His left common femoral artery was widely patent (AP and transverse diameter of 8-9mm throughout), but the right was only 4-5mm throughout.

In the meantime, his peak airway pressures were consistently between 35 and 40cmH2O, despite tidal volumes of 230ml, 3.8ml/kg). With a rate of 32-35 breaths per minute, his pH was  initially maintained above 7.2, with a pCO2 of 9-11kPa. Over the course of the next few hours, this became increasingly difficult to achieve. His oxygen requirements did not escalate (an FiO2 of 0.6 provided a pO2 of 8-9kPa). When his pCO2 increased to 15.4kPa and his pH dropped to 7.17, further adjustments were made and the PEEP decreased to 5cmH2O from 10cmH2O. His noradrenaline requirements were increasing and with the aid of the cardiac output monitoring, he was cautiously given fluid with a good response.

He was transferred to the centre in which a lung transplant could be performed within hours of the referral. A Novalung device was inserted and he underwent a bilateral lobar lung transplant several days later. He was in hospital for 6 weeks and made a very good long-term recovery. At six months, he was extremely well and was undertaking his activities of daily living completely normally with stable lung function. He even managed to complete an eight mile bike ride.

What is the rationale for extracorporeal lung assist?
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Transplantation After Brainstem Death

A 38-year-old previously fit man suffered a grade five subarachnoid haemorrhage. Attempts at coiling failed and he suffered a catastrophic rebleed on-table whereupon his pupils became fixed and dilated. After a suitable sedation washout period he underwent testing which confirmed brainstem death at which point he was referred to the specialist nurse for organ donation. Following counselling of the family and appropriate assessment, donation of his kidneys, liver and heart was agreed.

Upon confirmation of brainstem death, mechanical ventilation was continued to ensure PaO2 greater than 10 kPa and limit peak inflation pressure to less than 30 cmH20. Vasoactive support was switched from noradrenaline to vasopressin 0.02 iu/kg/min. Methylprednisolone and intravenous triiodothyronine were administered whilst awaiting harvest. Blood antibody testing for HIV1+2, Hepatitis B and C, HTLV-1 and CMV IgG were all negative. A transthoracic echocardiogram confirmed good biventricular function; following discussion with the transplant retrieval team a pulmonary artery catheter was floated. Clinical measurements of cardiac output and mixed venous oxygen saturation were satisfactory. Adequate hydration was maintained with crystalloid by infusion and glucose control optimised in the range 8-10 mmol/L with insulin. The dedicated retrieval team performed the organ retrieval eighteen hours after confirmation of brainstem death.

How can we optimise organ function for organ donation?Read More »

High Dose Insulin Infusion for Calcium Channel Blocker Overdose

A 24-year-old was admitted following an intentional overdose of 10mg amlodipine tablets following an argument with his family. Approximately 10 tablets were ingested. On self-presentation two hours after the event, he was clinically stable with no haemodynamic compromise. There was no airway or respiratory compromise and a 12 lead electrocardiogram demonstrated sinus rhythm at 98 beats per minute. Both an arterial blood gas and electrolyte analysis were normal. Ionised calcium was 1.14 mol/L.

Over the following two hours he developed hypotension down to a nadir of 58/32 mmHg without change in heart rate or rhythm or the development of metabolic abnormalities. This was initially treated with intravenous fluids without significant response. A bolus of calcium chloride was administered without success; at this time he was referred to the intensive care team for assessment. Careful clinical examination revealed no other abnormality except hypotension. Neurological function remained intact and there appeared to be a vasodilated state with warm peripheries and relative tachycardia at 110 beats per minute in sinus rhythm.

The patient was transferred to the intensive care unit where an infusion of noradrenaline was commenced, rapidly escalating to a rate of 0.92 mcg/kg/min with little improvement in mean arterial pressure beyond 30-40 mmHg and relative oliguria. After consultation with the National Poisons Service, a high dose infusion of actrapid was commenced at rate of 0.5 units/kg/hour, with subsequent improvement of his haemodynamic parameters and a reduction in his noradrenaline requirement. Over the following 4 hours, both this infusion and the noradrenaline infusion were subsequently weaned off. The patient was discharged to the ward after eight hours and after assessment by the psychiatric team, from hospital the following day.

What are the clinical features of calcium channel blocker overdose and what is the role of high dose insulin infusion?Read More »

Attempted Suicide and Treatment Withdrawal

A elderly man  was found unconscious at home having taken an overdose of prescription medication. This event may have been precipitated by a recent bereavement and worsening of his preexisting depression for which he had recently been reviewed by psychiatric services and commenced on an SNRI. He left a note at the scene of the suicide attempt, clearly stating that he intended to take his own life and did not wish to be resuscitated in the event of being found alive. He was discovered in his home by a relative who had been growing increasingly concerned as to his welfare, having not spoken to him for several days. On arrival in ED his Glasgow coma score (GCS) was 3/15. He was known to be taking venlafaxine for depression and amitriptyline for chronic back pain, and empty packets of each drug were found at his home.

He was intubated and transferred to the intensive care unit. Supportive care was provided including vasopressors (noradrenaline) for hypotension, electrolyte correction and ventilatory support. Plain chest radiograph showed a probable aspiration pneumonitis affecting the right upper and middle lobe. He was hypoxic with a high Fi 02 requirement and needed high levels of PEEP to maintain adequate oxygenation. His conscious level fluctuated over several days and he became increasingly agitated and exhibited signs of distress. At this stage it was not clear if he was orientated in time, place or person. He underwent percutaneous tracheostomy to facilitate weaning and reduce sedation requirements.

We were then able to wean him from sedation by day 11 of his admission. The patient’s ventilatory requirements were still high requiring mean airway pressures of 30 cmH2O, PEEP of 10 cmH2O, and an inspired oxygen concentration of 60%. At this stage he indicated to the ITU team that he did not wish treatment to be continued. We found him to be fully orientated in terms of time and place and he was aware of the preceding events and his intentional overdose. It was clearly explained to him that if treatment were discontinued he would die. He indicated to us that he had no intention of changing his mind.

We referred him to the liaison psychiatrist for the hospital who independently assessed and found him to be competent and able to fully understand the implications of such a decision, i.e. his likely death from respiratory failure. The psychiatrist also found him to be depressed but noted that this did not interfere with his competence and ability to give or withhold his consent. With his consent, his family were informed of this development. They had been agonizing for some time over whether they had made the right decision to call emergency services when they first found him. They attempted to dissuade him but his resolve was unshakeable. Invasive ventilation was withdrawn on the morning of his 15th day of ITU as per his wishes. Diamorphine was administered to reduce symptoms of respiratory distress. He died of hypoxia later that day. Cause of death was recorded as aspiration pneumonia.

Describe the ethical and legal framework utilised in the management of this patient.Read More »

Major Haemorrhage and Recombinant Factor VIIa Concentrate

Major Haemorrhage and Recombinant Factor VIIa Concentrate

A 40-year-old female intravenous drug user presented with a diffusely swollen right lower leg. She had injected heroin into her right thigh one week previously. The swelling started 3 days later. Initial observations revealed T 39.6, HR 135, NIBP 100/87, RR 32, Sats 96% on air. On examination, she was pale and sweaty. She had a swollen right lower leg with mottling of her foot and poor pedal pulses. Following initial fluid resuscitation, chest X-ray, cultures and broad-spectrum antibiotics (Flucloxacillin, Metronidazole and Gentamicin), she underwent CT angiogram of her lower limbs which showed oedematous and expanded muscle compartments of the thigh and calf but patent arterial flow to the feet. There was also right common femoral vein thrombosis with some vessel patency. Initial labs revealed neutrophilia (9.2), thrombocytopaenia (16) and deranged coagulation (PT 16, APPT 33, Fib 2.6). CK was 57000. She underwent right leg fasciotomies and was brought to ICU ventilated and on Noradrenaline to maintain MAP >65. She commenced Immunoglobulin IV 1gram/kg per day for 2 days for suspected Streptococcus Group A sepsis. That night she had massive transfusion requirements due to ongoing haemoserous ooze from her fasciotomy sites, losing up to 1 litre of haemoserous fluid per hour. Overnight she received 10 units RCC, 8 x FFP, 6 x Platelets and 2 x Cryoprecipitate, as well as Vitamin K (guided by Hb on ABG, formal lab results and thromboelastography). She was discussed with the Haematology Consultant and it was decided that, if rapid blood loss continued despite full correction of her clotting factors, fibrinogen and platelets then Factor VII could be given. However, over the next 2 hours, losses were much reduced following product replacement, and since she already had clot in her femoral vein, Factor VII Concentrate was not given.

What is the role of Recombinant Factor VIIa in major haemorrhage?

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Rapid Response Systems

Rapid Response Systems

An elderly man was admitted with an acute abdomen and free air visible under the diaphragm on CXR. He was fluid resuscitated before undergoing emergency laparotomy, where a perforated duodenal ulcer was oversewn. He was admitted to ICU postoperatively, extubated the next morning and deemed fit for discharge to the surgical ward later that day. Due to a lack of surgical beds, he was eventually discharged from ICU at 22:30. Eight hours post discharge, he was urgently re-referred to ICU after being found moribund on the ward. Before he could be seen and assessed he suffered an unrecoverable asystolic arrest. Review of his observation charts showed that there had been a clear deterioration in recorded observations, including hypotension for the two preceeding hours. However, the Early Warning Score had been calculated incorrectly, and no escalation had occurred.

What evidence is there that rapid response systems are effective in preventing patient deterioration and improving outcomes?

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Nutrition in Acute Pancreatitis

Nutrition in Acute Pancreatitis

A 55-year-old previously healthy lady was admitted with pancreatitis secondary to gallstones. Her admission modified Glasgow Score was 4, and CT scan showed approximately 70% necrosis of the pancreas encompassing the neck, body and tail with sparing of the head. She rapidly developed ARDS, AKI and vasoplegia, and subsequently developed abdominal compartment syndrome requiring decompressive laparotomy. Her later complications included intraabdominal collections requiring percutaneous drainage, upper GI bleeding, and staged closure of her laparostomy. She was initially commenced on enteral NG feeding but developed high NG aspirates despite pro-kinetics. Parenteral nutrition (PN) was commenced in combination with a ‘trophic’ enteral feed. Four weeks into her admission her triglyceride level was found to be elevated, necessitating lipid free PN and cessation of propofol. This led to a drop in her triglyceride level.

How should we manage the provision of nutrition in acute pancreatitis?

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ICU Admission with Haematological Malignancy

Outcomes of ICU Admission with Haematological Malignancy

An middle aged woman presented with a blast crisis following acute transformation of preexisting chronic myelomonocytic leukaemia. She failed to respond to several cycles of chemotherapy and underwent allogeneic bone marrow transplant. She subsequently developed neutropaenic septic shock and was found to have fungal pulmonary abscesses. Her sepsis was aggressively managed on ICU and she made steady progress and eventually recovered, and was discharged from hospital 5 weeks after her ICU admission.

What is the current evidence related to the mortality and morbidity associated with admission to intensive care for patients with haematological malignancy?Read More »

ECMO for Severe Refractory Hypoxaemia

ECMO for Severe Refractory Hypoxaemia

An 60 year old woman developed ARDS secondary to pneumococcal meningitis. Despite optimal ventilatory management and restrictive fluid intake her oxygenation remained severely impaired. She was referred to the regional respiratory failure unit who established her on mobile ECMO for retrieval. She remained on ECMO for five days, weaned off the ventilator after three further days and made a full neurological recovery leaving hospital two weeks later.

Is there sufficient evidence to promote the use of Extracorporeal Membrane Oxygenation (ECMO) for the management of severe refractory hypoxia in the United Kingdom?Read More »