Intraventricular Alteplase

Intraventricular Alteplase

  1. Prepare alteplase [concentration 1 mg/1 mL] with preservative-free saline.
  2. Combine 1 mL of alteplase [concentration 1 mg/1 mL] with 2 mL saline (total 3 mL).
  3. Remove 1-2 mL CSF from EVD.
  4. Administer 3 mL alteplase + saline solution into EVD.
  5.  Clamp EVD for 30 minutes following administration, then open EVD.
  6. Repeat administration, if required, at 8-12 hours’ interval.

*Thanks Dr. Ben Lo (LHH Neurointensivist / Neurosurgeon) for this protocol.

Diabetes Care in the Hospital

A1C should be measured on all patients with diabetes or hyperglycemia admitted to the hospital if the test has not been performed in the previous 3 months.

There is evidence to support preadmission treatment of hyperglycemia in patients scheduled for elective surgery as an effective means of reducing adverse outcomes.

Hyperglycemia in hospitalized patients is defined as blood glucose >140mg/dL.

Glycemic Targets in Hospitalized Patients:

  • Insulin therapy should be initiated for persistent hyperglycemia >= 180mg/dL
  • Once insulin therapy is started, a target glucose range of 140-180mg/dL is recommended for majority of patients.
  • More stringent goals (110-140mg/dL) may be appropriate for selected patients (e.g. critically ill post-surgical patients or patients with cardiac surgery) if they can be achieved without significant hypoglycemia.
  • >180mg/dL may be acceptable in terminally ill patients, patients with severe comorbities and inpatient care settings where frequent glucose monitoring or close nursing supervision is not feasible.

The Van den Berghe trial and the NICE-SUGAR Trial

Insulin Dose

Patients with type 1 diabetes should continue receiving basal insulin even if feedings are discontinued.

Estimate basal needs from preadmission dose of long-acting or intermediate insulin, or a percentage of total daily requirements established in the hospital (30-50% total daily dose of insulin)

In the absence of previous insulin dosing, reasonable starting point is NPH / detemir insulin 5 units q12h or insulin glaring 10 units daily.

Patients on continuous tube feeds – total daily nutritional component = 1 unit insulin for every 10-15g CHO per day or %total daily dose when patient is being fed (40-70% total daily dose of insulin)

Patients on bolus tube feeds – 1 units regular or rapid acting insulin per 10-15g CHO given SQ before each feeding.

Patients receiving TPN – add regular insuli to solution, esp if >20 u coverage required in past 24 hours; starting dose of 1 units regular insulin for every 10g dextrose recommended. Adjust daily in the solution.

HYPOGLYCEMIA

Hypoglycemia is categorized by blood glucose concentration and clinical correlates.

  • Level 1 – 54-70mg/dL
  • Level 2 – <54 mg/dL (threshold for neuroglycopenic symptoms)
  • Level 3 – clinical event characterized by AMS and/or physical functioning requiring assistance from another person

Patient treatment regimen should be reviewed anytime a blood glucose value of <70mg/dL occurs. Such readings predict subsequent level 3 hypoglycemia.

AKI is an important risk factor for hypoglycemia in the hospital.

Other causes of hypoglycemia: sudden reduction of steroids, reduced PO intake, remains, inappropriate timing of rapid-acting insulin in relation to meals, reduced infusion rate of IV dextrose, unexpected interruption of tube feeds / TPN; altered ability of patient to report symptoms..

Continuous Glucose Monitoring

Several studies have shown that CGM use did not improve glucose control but detected a greater number of hypoglycemic events. There is currently insufficient data on clinical outcomes, safety or costs effectiveness to recommend use of CGM in hospitalized patients.

Insulin Therapy:

Basal insulin or basal plus bolus correction regimen is the preferred treatment for patients that are NPO.

Insulin regimen with basal, pyramidal and correction components is preferred for patients with good nutritional intake.

If oral intake is poor, safer procedure is to administer pyramidal insulin immediately after the patient eats, with the dose adjusted to be appropriate for the amount ingested.

Use of premix insulin formulations in the hospital (70/30 NPH/regular insulin) showed significantly increased hypoglycemia. Not routinely recommended for in-patient use.

Transitioning

Transitioning from IV infusion to subcutaneous regimen – give subcutaneous basal linsulin 2-4h before drip is discontinued. Convert to basal insulin at 60-80% of daily infusion dose.

Safe Discharge

If oral medications are held in the hospital, there should be a protocol for resuming them 1-2 days before discharge.

Schedule out-patient f/u with primary care provider or endocrinologist or DM educator within 1 month for all patients with hyperglycemia.

If glycemicc medications are changed of glucose control not optional at discharge, earlier appointment (1-2 weeks) preferred.

Perioperative Care:

  • Target 80-180mg/dL
  • Metformin should be withheld on day of surgery
  • Withhold any other oral glucose-lowering agents the morning of surgery; given half of NPH dose or 60-80% doses of long acting analog or pump basal insulin.
  • Monitor finger sticks q4-6h while NPO and dose with short- or rapid-acting insulin PRN
  • Reduction of insulin given the night before surgery by ~25% likely to achieve perioperative blood glucose levels in target range with lower risk of hypoglycemia

Reference:

15. Diabetes Care in the Hospital: Standards of Medical Care in Diabetes—2020. (2019). Diabetes Care, 43(Supplement 1), pp.S193-S202.

Fluid Overload

Great infographic showing the pathological consequences of fluid overload. We should be mindful of our fluid boluses. And we wonder why patients have ileus, why the creatinine is rising, why the patient cannot be weaned from the ventilator.

Changing fluid resuscitation strategies parallel the phases of critical illness and the immune response to sepsis or another injury.

Phase A (0-6 hours): initial aggressive volume resuscitation (eg, 30 mL/kg of intravenous crystalloid), also known as the ebb phase of critical illness. Phase B (6-36 hours): decelerating fluid resuscitation; fluid is often still required to compensate for extravascular sequestration, but fluids should only be provided as needed to maintain organ perfusion in a targeted manner, with frequent reassessment of fluid responsiveness. Phase C (36-48 hours): equilibrium phase; fluid administration is stopped. Phase D (beyond 48 hours): mobilization, deresuscitation, or flow phase; fluids are withheld to allow for spontaneous diuresis or, in those who fail to autodiurese, pharmacologic diuresis or ultrafiltration can be provided to achieve euvolemia. The time at which a given patient transitions phases may vary and multiple insults can substantially disrupt this sequence.

Note: Should we have parallel phases in fluid management in subarachnoid hemorrhage?

Reference:

Griffin, B., Liu, K. and Teixeira, J. (2020). Critical Care Nephrology: Core Curriculum 2020. American Journal of Kidney Diseases.

Vasoactive Agents

Classification of Vasoactive Agents

Type and strength of the vascular response of the vasoactive agents

Adrenergic inoconstrictors stimulate β1 and α1 receptors to induce increased inotropy and vasoconstriction, respectively.

Epinephrine, in addition to β1 and α1 activity, has significant β2 activity, but acts as a vasoconstrictor due to the dominant effect of α1-mediated vasoconstriction; however, β2-mediated relaxation of smooth muscle by epinephrine is clinically important in the setting of anaphylaxis, where it acts to induce bronchodilation.

Pure vasoconstrictors include the pure α1 agonist phenylephrine and the nonadrenergic agent vasopressin, which acts on V1receptors on vascular smooth muscle cells; angiotensin II (not depicted) is a second recently approved nonadrenergic pure vasoconstrictor that acts on AT1 receptors on vascular smooth muscle.

Inodilators include dobutamine, which increases inotropy via β1 stimulation and induces vasodilation via vascular β2receptors; milrinone acts similarly via phosphodiesterase 3 inhibition.

Effects in the case of epinephrine and dopamine depend in part on dose.

Reference:

Griffin, B., Liu, K. and Teixeira, J. (2020). Critical Care Nephrology: Core Curriculum 2020. American Journal of Kidney Diseases.

2019-nCoV: A New Betacoronavirus

2019 novel coronavirus (2019-nCoV)

What are Coronaviruses?

Coronaviruses are enveloped, non-segmented positive-sense RNA viruses belonging to the family Coronaviridae and the order Nidovirales.

The coronaviruses are broadly distributed in humans and other mammals

Most coronavirus infections are mild (hCoV-229E, OC43, NL63, HKU1)

Recently, epidemics of coronaviruses have occurred, particularly:

– MERS-CoV – Middle East respiratory syndrome

– SARS-CoV – severe acute respiratory syndrome

Both account for >10K cumulative cases, and Mortality rates are high (i.e. 10% SARS, 37% MERS).

How did the 2019-nCoV infections start?

Recently, a cluster of pneumonia cases of unknown causes have been detected in Wuhan, China. Most of these patients shared a history of exposure to Huanan seafood market and subsequently developed severe pneumonia. An alert for this cluster of cases was released by Chinese local health authority on 12/31/2019, and the market was shut down on 01/01/2020.

How was the 2019-nCoV cases managed initially?

59 suspected cases of pneumonia of unknown cause was transferred to a designated hospital (Jin Yintan Hospital), where an expert team of physicians, epidemiologists, virologists and government officials was formed to oversee these cases.

The diagnosis was initially based on clinical characteristics, chest imaging, and ruling out common bacterial and viral pathogens

Suspected cases were isolated, with airborne precautions.

A novel coronavirus was eventually isolated from specimen collected from the lower respiratory tract and diagnostic test developed.

What diagnostic tests should be performed for suspected 2019-nCoV?

Initial investigations should include CBC, coagulation profile, metabolic profile (renal and liver function tests, creating kinase, LDH, electrolytes)

Respiratory specimens (nasal/ pharyngeal swabs, BAL fluid, sputum, bronchial aspirated) should be tested for common viruses (influenza, avian influenza, RSV, adenovirus, parainfluenza, SARS-CoV, MERS-CoV) using real-time RT PCR assays

Routine bacterial and fungal examinations should be performed

2019-nCoV infection should be confirmed by real-time RT-PCR and next-generation sequencing.

What are the common laboratory findings in 2019-nCoV?

Leukopenia( 25%), lymphopenia (63%), transaminitis (37%), increased troponin I (?). Prothrombin time and D-dinner levels on admission noted to be higher in patients that were admitted to ICU.

How is 2019-nCoV treated?

Empiric antibiotics (PO or IV antibiotics / oseltamivir 75mg PO BID) should be started prior to results of initial work-up.

Treatment is mainly supportive. Oxygen support, including mechanical ventilation is frequently necessary.

Should steroids be given?

Steroids (methylprednisolone 40-120mg/day) were initially administered to patients suspected of 2019-nCoV infection with severe symptoms.

In view of high amounts of cytokines induced by SARS MERS and 2019-nCoV, steroids have been used frequently for treatment with severe illness. Current evidence in SARS and MERS suggests that steroids did not have effect on mortality, but rather delayed viral clearance. Until we have evidence of efficacy, steroids should not be routinely given.

Can we use antiviral drugs to treat 2019-nCoV?

No antiviral treatment has been proven to be effective.

Lopinavir + ritonavir associated with substantial clinical benefit (fewer adverse outcomes) in the treatment of SARS

IFN B1b, lopinavir and ritonavir being tested for MERS

Remdesivir is potentially efficacious for MERS / SARS based on preclinical evidence.

Other Notes:

In the cohort of 41 patients reported in Lancet journal:

73% were men, median age 49 years old, and 32% had underlying diseases (DM HTN CAD). Biggest risk factor was exposure to Huanan seafood market (66%)

Most common symptoms were fever (98%), cough (76%), myalgia / fatigue (44%). Typical symptoms of viral respiratory infection.

Less common symptoms include sputum production (28%), headaches (8%), hemoptysis (5%), diarrhea (3%).

All patients had PNA with abnormal findings on chest CT

Complications include ARDS (29%), acute cardiac injury (12%), secondary infection (10%).

32% wold require ICU admission.

First fatal case – had continuous exposure to the marketed, was admitted to fro 7-day history of fever, cough suspense. 5 days after illness, wife with no exposure to market, presented with PNA and hospitalized.

Median time from onset to first hospital admission was 7 days, to SOB was 8 days, to ARDS was 9 days and to mech ventilation was 10.5 days and to ICU admission was 10.5 days.

Is there a role for procalcitonin in management of 2019-nCoV?

In this cohort, most patients had normal serum procalcitonin. 3 of 4 patients who developed secondary infection had procalcitonin >0.5ng/mL.

What are the common abnormalities noted on CT chest?

CT chest abnormalities were detected among all patients. 98% had bilateral lung involvement. Typical findings on chest CT include bilateral multiple lobular and subsegmental areas of consolidation.

What is the mortality rate of 2019-nCoV infection?

In this series, 68% were discharged and 15% died.

What is the criteria for discharge?

In this series, patients were discharged after being afebrile x 10days, with improved CXR findings and oral clearance of the virus in the respiratory samples from the upper respiratory tract

How is this virus transmitted?

Evidence indicates human transmission. Concern that the virus could have acquired the ability for efficient human transmission.

Note: few patients had prominent upper respiratory tract signs and symptoms (rhinorrhea, sneezing, sore throat) which indicates that the target cells might be located in the lower airway. Intestinal SSx (diarrhea) also rare.

Fecal and urine samples should be tested to exclude a potential alternative route of transmission that is unknown.

Both SARS and MERS originated in bats and transmitted directly to humans from market civets and dromedary camels, respectively

Onset of fever and respiratory symptoms in health care workers should be closely monitored.

References:

Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., Cheng, Z., Yu, T., Xia, J., Wei, Y., Wu, W., Xie, X., Yin, W., Li, H., Liu, M., Xiao, Y., Gao, H., Guo, L., Xie, J., Wang, G., Jiang, R., Gao, Z., Jin, Q., Wang, J. and Cao, B. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet.